POLYPEPTIDES AND NUCLEIC ACIDS FOR BOLEKINE

Abstract: The present invention is directed to Bolekine polypeptides and to nucleic acid molecules encoding those polypeptides. Also provided herein are vectors and host cells comprising those nucleic acid sequences, chimeric polypeptide molecules comprising the polypeptides of the present invention fused to heterologous polypeptide sequences, antibodies which bind to the polypeptides of the present invention and to methods for producing the polypeptides of the present invention.

Description: POLYPEPTIDES AND NUCLEIC ACIDS FOR BOLEKINE FIELD OF THE INVENTION The present invention relates generally to the identification and isolation of novel DNA and to the recombinant production of novel polypeptides . The invention also relates to methods of use of Bolekine and its role in the immune system and cell differentiation. BACKGROUND OF THE INVENTION Leukocytes include monocytes, macrophages, basophils, and eosinophils and play an important role in the immune response. These cells are important in the mechanisms initiated by T and/or B lymphocytes and secrete a range of cytokines which recruit and activate other inflammatory cells and contribute to tissue destruction. Thus, investigation of the regulatory processes by which leukocytes move to their appropriate destination and interact with other cells is critical. Currently, leukocytes are thought to move from the blood to injured or inflamed tissues by rolling along the endothelial cells of the blood vessel wall. This movement is mediated by transient interactions between selectins and their ligands. Next, the leukocyte must move through the vessel wall and into the tissues. This diapedesis and extravasation step involves cell activation which promotes a more stable leukocyte-endothelial cell interaction, again mediated by integrins and their ligands. Chemokines are a large family of structurally related polypeptide cytokines. These molecules stimulate leukocyte movement and may explain leukocyte trafficking in different inflammatory situations. Chemokines mediate the expression of particular adhesion molecules on endothelial cells, and they produce chemoattractants which activate specific cell types. In addition, ihe chemokines stimulate proliferation and regulate activation of specific cell types. In both of these activities, chemokines demonstrate a high degree of target cell specificity. The chemokine family is divided into two subfamilies based on whether two amino terminal cysteine residues are immediately adjacent (C-C) or separated by one amino acid (C-X-C). Chemokines of the C-X-C family generally activate neutrophils and fibroblasts while the C-C chemokines act on a more diverse group of target cells including monocytes/macrophages, basophils, eosinophils and T lymphocytes. The known chemokines of both subfamilies are synthesized by many diverse cell types as reviewed in Thomson A. (1994) The Cytokine Handbook, 2 d Ed. Academic Press, N.Y. Chemokines are also reviewed in Schall TJ (1994) Chemotactic Cytokines: Targets for Therapeutic Development. International Business Communications, Southborough Mass. pp 180-270; and in Paul WE (1993) Fundamental Immunology, 3rd Ed. Raven Press, N.Y. pp 822-826. Known chemokines of the C-X-C subfamily include macrophage inflammatory proteins alpha and beta (MIP-1 and MIP-2 ), interleukin-8 (IL-8), and growth regulated protein (GRO-alpha and beta). MIP-2 was first identified as a 6 kDa heparin binding protein secreted by the mouse macrophage cell line RAW 264.7 upon stimulation with lipopolysaccharide (LPS). MIP-2 is a member of the C-X-C (or CXC) subfamily of chemokines. Mouse MIP-2 is chemotactic for human neutrophils and induces local neutrophil infiltration when injected into the foot pads of mice. Rat MIP-2 shows 86% amino acid homology to the mouse MIP-2 and is chemotactic for rat neutrophils but does not stimulate migration of rat alveolar macrophages or human peripheral blood eosinophils or lymphocytes. In addition, the rat MIP-2 has been shown to stimulate proliferation of rat alveolar epithelial cells but not fibroblasts. Current techniques for diagnosis of abnormalities in inflamed or diseased issues mainly rely on observation of clinical symptoms or serological analyses of body tissues or fluids for hormones, polypeptides or various metabolites . Problems exist with these diagnostic techniques . First, patients may not manifest clinical symptoms at early stages of disease. Second, serological tests do not always differentiate between invasive diseases and genetic syndromes. Thus, the identification of expressed chemokines is important to the development of new diagnostic techniques, effective therapies, and to aid in the understanding of molecular pathogenesis. To date, chemokines have been implicated in at least the following conditions: psoriasis, inflammatory bowel disease, renal disease, arthritis, immune-mediated alopecia, stroke, encephalitis, MS, hepatitis, and others. In addition, non-ELR-containing chemokines have been implicated in the inhibition of angiogenesis, thus indicating that these chemokines have a role in tumor vascularization and tumorigenesis. Therefore it is the object of this invention to identify polypeptides and nucleic acids encoding the same which have sequence identity and similarity with cytokine-induced neutrophil chemoattractants, such as MJJP-1, MEP-2, and other related proteins. We herein describe the identification and characterization of novel chemokine family polypeptides, designated herein as Bolekine polypeptides. SUMMARY OF THE INVENTION In one embodiment, the invention provides an isolated nucleic acid molecule comprising a nucleotide sequence that encodes a Bolekine polypeptide. In one aspect, the isolated nucleic acid molecule comprises a nucleotide sequence having at least about 80% nucleic acid sequence identity, alternatively at least about 81 % nucleic acid sequence identity, alternatively at least about 82% nucleic acid sequence identity, alternatively at least about 83 % nucleic acid sequence identity, alternatively at least about 84% nucleic acid sequence identity, alternatively at least about 85% nucleic acid sequence identity, alternatively at least about 86 % nucleic acid sequence identity, alternatively at least about 87 % nucleic acid sequence identity, alternatively at least about 88% nucleic acid sequence identity, alternatively at least about 89% nucleic acid sequence identity, alternatively at least about 90% nucleic acid sequence identity, alternatively at least about 91 % nucleic acid sequence identity, alternatively at least about 92% nucleic acid sequence identity, alternatively at least about 93 % nucleic acid sequence identity, alternatively at least about 94% nucleic acid sequence identity, alternatively at least about 95% nucleic acid sequence identity, alternatively at least about 96% nucleic acid sequence identity, alternatively at least about 97% nucleic acid sequence identity, alternatively at least about 98% nucleic acid sequence identity and alternatively at least about 99% nucleic acid sequence identity to (a) a DNA molecule encoding a Bolekine polypeptide having a full-length amino acid sequence as disclosed herein, an amino acid sequence lacking the signal peptide as disclosed herein, an extracellular domain of a transmembrane protein, with or without the signal peptide, as disclosed herein or any other specifically defined fragment of the full-length amino acid sequence as disclosed herein, or (b) the complement of the DNA molecule of (a). In other aspects , the isolated nucleic acid molecule comprises a nucleotide sequence having at least about 80% nucleic acid sequence identity, alternatively at least about 81 % nucleic acid sequence identity, alternatively at least about 82% nucleic acid sequence identity, alternatively at least about 83 % nucleic acid sequence identity, alternatively at least about 84% nucleic acid sequence identity, alternatively at least about 85% nucleic acid sequence identity, alternatively at least about 86% nucleic acid sequence identity, alternatively at least about 87% nucleic acid sequence identity, alternatively at least about 88% nucleic acid sequence identity, alternatively at least about 89% nucleic acid sequence identity, alternatively at least about 90% nucleic acid sequence identity, alternatively at least about 91 % nucleic acid sequence identity, alternatively at least about 92% nucleic acid sequence identity, alternatively at least about 93 % nucleic acid sequence identity, alternatively at least about 94% nucleic acid sequence identity, alternatively at least about 95 % nucleic acid sequence identity, alternatively at least about 96% nucleic acid sequence identity, alternatively at least about 97% nucleic acid sequence identity, alternatively at least about 98% nucleic acid sequence identity and alternatively at least about 99% nucleic acid sequence identity to (a) a DNA molecule comprising the coding sequence of a full-length Bolekine polypeptide cDNA as disclosed herein, the coding sequence of a Bolekine polypeptide lacking the signal peptide as disclosed herein, the coding sequence of an extracellular domain of a transmembrane Bolekine polypeptide, with or without the signal peptide, as disclosed herein or the coding sequence of any other specifically defined fragment of the full-length amino acid sequence as disclosed herein, or (b) the complement of the DNA molecule of (a). In a further aspect, the invention concerns an isolated nucleic acid molecule comprising a nucleotide sequence having at least about 80% nucleic acid sequence identity, alternatively at least about 81 % nucleic acid sequence identity, alternatively at least about 82 % nucleic acid sequence identity, alternatively at least about 83 % nucleic acid sequence identity, alternatively at least about 84% nucleic acid sequence identity, alternatively at least about 85% nucleic acid sequence identity, alternatively at least about 86% nucleic acid sequence identity, alternatively at least about 87% nucleic acid sequence identity, alternatively at least about 88% nucleic acid sequence identity, alternatively at least about 89 % nucleic acid sequence identity, alternatively at least about 90 % nucleic acid sequence identity, alternatively at least about 91 % nucleic acid sequence identity, alternatively at least about 92% nucleic acid sequence identity, alternatively at least about 93% nucleic acid sequence identity, alternatively at least about 94% nucleic acid sequence identity, alternatively at least about 95% nucleic acid sequence identity, alternatively at least about 96 % nucleic acid sequence identity, alternatively at least about 97 % nucleic acid sequence identity, alternatively at least about 98% nucleic acid sequence identity and alternatively at least about 99% nucleic acid sequence identity to (a) a DNA molecule that encodes the same mature polypeptide encoded by any of the human protein cDNAs deposited with the ATCC as disclosed herein, or (b) the complement of the DNA molecule of (a). Another aspect the invention provides an isolated nucleic acid molecule comprising a nucleotide sequence encoding a Bolekine polypeptide which is either transmembrane domain-deleted or transmembrane domain-inactivated, or is complementary to such encoding nucleotide sequence, wherein the transmembrane domain(s) of such polypeptide are disclosed herein. Therefore, soluble extracellular domains of the herein described Bolekine polypeptides are contemplated. Another embodiment is directed to fragments of a Bolekine polypeptide coding sequence, or the complement thereof, that may find use as, for example, hybridization probes, for encoding fragments of a Bolekine polypeptide that may optionally encode a polypeptide comprising a binding site for an anti-Bolekine antibody or as antisense oligonucleotide probes. Such nucleic acid fragments are usually at least about 10 nucleotides in length, alternatively at least about 15 nucleotides in length, alternatively at least about 20 nucleotides in length, alternatively at least about 30 nucleotides in length, alternatively at least about 40 nucleotides in length, alternatively at least about 50 nucleotides in length, alternatively at least about 60 nucleotides in length, alternatively at least about 70 nucleotides in length, alternatively at least about 80 nucleotides in length, alternatively at least about 90 nucleotides in length, alternatively at least about 100 nucleotides in length, alternatively at least about 110 nucleotides in length, alternatively at least about 120 nucleotides in length, alternatively at least about 130 nucleotides in length, alternatively at least about 140 nucleotides in length, alternatively at least about 150 nucleotides in length, alternatively at least about 160 nucleotides in length, alternatively at least about 170 nucleotides in length, alternatively at least about 180 nucleotides in length, alternatively at least about 190 nucleotides in length, alternatively at least about 200 nucleotides in length, alternatively at least about 250 nucleotides in length, alternatively at least about 300 nucleotides in length, alternatively at least about 350 nucleotides in length, alternatively at least about 400 nucleotides in length, alternatively at least about 450 nucleotides in length, alternatively at least about 500 nucleotides in length, alternatively at least about 600 nucleotides in length, alternatively at least about 700 nucleotides in length, alternatively at least about 800 nucleotides in length, alternatively at least about 900 nucleotides in length and alternatively at least about 1000 nucleotides in length, wherein in this context the term "about" means the referenced nucleotide sequence length plus or minus 10% of that referenced length. It is noted that novel fragments of a Bolekine polypeptide-encoding nucleotide sequence may be determined in a routine manner by aligning the Bolekine polypeptide-encoding nucleotide sequence with other known nucleotide sequences using any of a number of well known sequence alignment programs and determining which Bolekine polypeptide-encoding nucleotide sequence fragment(s) are novel. All of such Bolekine polypeptide-encoding nucleotide sequences are contemplated herein. Also contemplated are the Bolekine polypeptide fragments encoded by these nucleotide molecule fragments, preferably those Bolekine polypeptide fragments that comprise a binding site for an anti-Bolekine antibody. In another embodiment, the invention provides isolated Bolekine polypeptide encoded by any of the isolated nucleic acid sequences hereinabove identified. In a certain aspect, the invention concerns an isolated Bolekine polypeptide, comprising an amino acid sequence having at least about 80% amino acid sequence identity, alternatively at least about 81 % amino acid sequence identity, alternatively at least about 82% amino acid sequence identity, alternatively at least about 83 % amino acid sequence identity, alternatively at least about 84% amino acid sequence identity, alternatively at least about 85% amino acid sequence identity, alternatively at least about 86% amino acid sequence identity, alternatively at least about 87% amino acid sequence identity, alternatively at least about 88% amino acid sequence identity, alternatively at least about 89% amino acid sequence identity, alternatively at least about 90% amino acid sequence identity, alternatively at least about 91 % amino acid sequence identity, alternatively at least about 92% amino acid sequence identity, alternatively at least about 93% amino acid sequence identity, alternatively at least about 94% amino acid sequence identity, alternatively at least about 95% amino acid sequence identity, alternatively at least about 96% amino acid sequence identity, alternatively at least about 97% amino acid sequence identity, alternatively at least about 98 % amino acid sequence identity and alternatively at least about 99% amino acid sequence identity to a Bolekine polypeptide having a full-length amino acid sequence as disclosed herein, an amino acid sequence lacking the signal peptide as disclosed herein, an extracellular domain of a transmembrane protein, with or without the signal peptide, as disclosed herein or any other specifically defined fragment of the full-length amino acid sequence as disclosed herein. In a further aspect, the invention concerns an isolated Bolekine polypeptide comprising an amino acid sequence having at least about 80% amino acid sequence identity, alternatively at least about 81 % amino acid sequence identity, alternatively at least about 82% amino acid sequence identity, alternatively at least about 83 % amino acid sequence identity, alternatively at least about 84% amino acid sequence identity, alternatively at least about 85% amino acid sequence identity, alternatively at least about 86% amino acid sequence identity, alternatively at least about 87% amino acid sequence identity, alternatively at least about 88% amino acid sequence identity, alternatively at least about 89 % amino acid sequence identity, alternatively at least about 90 % amino acid sequence identity, alternatively at least about 91 % amino acid sequence identity, alternatively at least about 92% amino acid sequence identity, alternatively at least about 93% amino acid sequence identity, alternatively at least about 94% amino acid sequence identity, alternatively at least about 95% amino acid sequence identity, alternatively at least about 96% amino acid sequence identity, alternatively at least about 97% amino acid sequence identity, alternatively at least about 98 % amino acid sequence identity and alternatively at least about 99% amino acid sequence identity to an amino acid sequence encoded by any of the human protein cDNAs deposited with the ATCC as disclosed herein. In a specific aspect, the invention provides an isolated Bolekine polypeptide without the N-terminal signal sequence and/or the initiating methionine and is encoded by a nucleotide sequence that encodes such an amino acid sequence as hereinbefore described. Processes for producing the same are also herein described, wherein those processes comprise culturing a host cell comprising a vector which comprises the appropriate encoding nucleic acid molecule under conditions suitable for expression of the Bolekine polypeptide and recovering the Bolekine polypeptide from the cell culture. Another aspect the invention provides an isolated Bolekine polypeptide which is either transmembrane domain-deleted or transmembrane domain-inactivated. Processes for producing the same are also herein described, wherein those processes comprise culturing a host cell comprising a vector which comprises the appropriate encoding nucleic acid molecule under conditions suitable for expression of the Bolekine polypeptide and recovering the Bolekine polypeptide from the cell culture. In yet another embodiment, the invention concerns agonists and antagonists of a native Bolekine polypeptide as defined herein. In a particular embodiment, the agonist or antagonist is an anti-Bolekine antibody or a small molecule. In a further embodiment, the invention concerns a method of identifying agonists or antagonists to a Bolekine polypeptide which comprise contacting the Bolekine polypeptide with a candidate molecule and monitoring a biological activity mediated by said Bolekine polypeptide. Preferably, the Bolekine polypeptide is a native Bolekine polypeptide. In a still further embodiment, the invention concerns a composition of matter comprising a Bolekine polypeptide, or an agonist or antagonist of a Bolekine polypeptide as herein described, or an anti-Bolekine antibody, in combination with a carrier. Optionally, the carrier is a pharmaceutically acceptable carrier. Another embodiment of the present invention is directed to the use of a Bolekine polypeptide, or an agonist or antagonist thereof as hereinbefore described, or an anti-Bolekine antibody, for the preparation of a medicament useful in the treatment of a condition which is responsive to the Bolekine polypeptide, an agonist or antagonist thereof or an anti-Bolekine antibody. In other embodiments of the present invention, the invention provides vectors comprising DNA encoding any of the herein described polypeptides. Host cell comprising any such vector are also provided. By way of example, the host cells may be CHO cells, E. coli, or yeast. A process for producing any of the herein described polypeptides is further provided and comprises culturing host cells under conditions suitable for expression of the desired polypeptide and recovering the desired polypeptide from the cell culture. In other embodiments, the invention provides ehimeric molecules comprising any of the herein described polypeptides fused to a heterologous polypeptide or amino acid sequence. Example of such ehimeric molecules comprise any of the herein described polypeptides fused to an epitope tag sequence or a Fc region of an immunoglobulin. In another embodiment, the invention provides an antibody which binds, preferably specifically, to any of the above or below described polypeptides. Optionally, the antibody is a monoclonal antibody, humanized antibody, antibody fragment or single-chain antibody. In yet other embodiments, the invention provides oligonucleotide probes which may be useful for isolating genomic and cDNA nucleotide sequences, measuring or detecting expression of an associated gene or as antisense probes, wherein those probes may be derived from any of the above or below described nucleotide sequences. Preferred probe lengths are described above. In yet other embodiments, the present invention is directed to methods of using the Bolekine polypeptides of the present invention for a variety of uses based upon the functional biological assay data presented in the Examples below. In yet other embodiments the invention is directed to methods that will increase the proliferation of immune cells such as presented in Example 10. In yet other embodiments the invention is directed to methods of use of increasing vascular permeability such as presented in Example 11. BRIEF DESCRIPTION OF THE DRAWINGS Figure 1 shows a nucleotide sequence (SEQ ID NO:l) of a native sequence Bolekine cDNA, wherein SEQ ID NO:l is a clone designated herein as Bolekine. Figure 2 shows the amino acid sequence (SEQ ID NO:2) derived from the coding sequence of SEQ ID NO:l shown in Figure 1. Figure 3 depicts the results of Northern blots analyzing the nucleic acid encoding Bolekine. Figures 4A through 4E are photomicrographs depicting the results of in situ hybridization assays performed on the nucleic acid encoding Bolekine. Figure 4A depicts fetal skin, in the right frame is dark field microscopy, displaying the in situ, in the left frame is normal bright field microscopy. Figure 4B depicts fetal kidney, in the right frame is dark field microscopy, displaying the in situ, in the left frame is normal bright field microscopy. Figure 4C depicts fetal gut, in the right frame is dark field microscopy, displaying the in situ, in the left frame is normal bright field microscopy. Figure 4D depicts adult gut, in the right frame is dark field microscopy, displaying the in situ, in the left frame is normal bright field microscopy. Figure 4E depicts cerebrum, in the right frame is dark field microscopy, displaying the in situ, in the left frame is normal bright field microscopy. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS I. Definitions The terms "Bolekine" as used herein encompass native sequence polypeptides and polypeptide variants (which are further defined herein). The Bolekine polypeptides described herein may be isolated from a variety of sources, such as from human tissue types or from another source, or prepared by recombinant or synthetic methods. The term "Bolekine polypeptide" refers to each individual Bolekine polypeptide disclosed herein. All disclosures in this specification which refer to the "Bolekine polypeptide" refer to each of the polypeptides individually as well as jointly. For example, descriptions of the preparation of, purification of, derivation of, formation of antibodies to or against, aαministration of, compositions containing, treatment of a disease with, etc., pertain to each polypeptide of the invention individually. The term "Bolekine polypeptide" also includes variants of the Bolekine polypeptides disclosed herein. A "native sequence Bolekine polypeptide" comprises a polypeptide having the same amino acid sequence as the corresponding Bolekine polypeptide derived from nature. Such native sequence Bolekine polypeptides can be isolated from nature or can be produced by recombinant or synthetic means. The term "native sequence Bolekine polypeptide" specifically encompasses naturally-occurring truncated or secreted forms of the specific Bolekine polypeptide (e.g., an extracellular domain sequence), naturally-occurring variant forms (e.g., alternatively spliced forms) and naturally-occurring allelic variants of the polypeptide. In various embodiments of the invention, the native sequence Bolekine polypeptides disclosed herein are mature or full-length native sequence polypeptides comprising the full-length amino acids sequences shown in the accompanying figures. Start and stop codons are shown in bold font and underlined in the figures. However, while the Bolekine polypeptide disclosed in the accompanying figures are shown to begin with methionine residues designated herein as amino acid position 1 in the figures , it is conceivable and possible that other methionine residues located either upstream or downstream from the amino acid position 1 in the figures may be employed as the starting amino acid residue for the Bolekine polypeptides. The Bolekine polypeptide "extracellular domain" or "ECD" refers to a form of the Bolekine polypeptide which is essentially free of the transmembrane and cytoplasmic domains. Ordinarily, a Bolekine polypeptide ECD will have less than 1 % of such transmembrane and/or cytoplasmic domains and preferably, will have less than 0.5% of such domains. It will be understood that any transmembrane domains identified for the Bolekine polypeptides of the present invention are identified pursuant to criteria routinely employed in the art for identifying that type of hydrophobic domain. The exact boundaries of a transmembrane domain may vary but most likely by no more than about 5 amino acids at either end of the domain as initially identified herein. Optionally, therefore, an extracellular domain of a Bolekine polypeptide may contain from about 5 or fewer amino acids on either side of the transmembrane domain/extracellular domain boundary as identified in the Examples or specification and such polypeptides, with or without the associated signal peptide, and nucleic acid encoding them, are comtemplated by the present invention. The approximate location of the "signal peptides" of the various Bolekine polypeptides disclosed herein are shown in the present specification and/or the accompanying figures. It is noted, however, that the C-terminal boundary of a signal peptide may vary, but most likely by no more than about 5 amino acids on either side of the signal peptide C-terminal boundary as initially identified herein, wherein the C-terminal boundary of the signal peptide may be identified pursuant to criteria routinely employed in the art for identifying that type of amino acid sequence element (e.g., Nielsen et al., Prot. Eng. 10:1-6 (1997) and von Heinje et al., Nucl. Acids. Res. 14:4683-4690 (1986)). Moreover, it is also recognized that, in some cases, cleavage of a signal sequence from a secreted polypeptide is not entirely uniform, resulting in more than one secreted species. These mature polypeptides, where the signal peptide is cleaved within no more than about 5 amino acids on either side of the C-terminal boundary of the signal peptide as identified herein, and the polynucleotides encoding them, are contemplated by the present invention. "Bolekine polypeptide variant" means an active Bolekine polypeptide as defined above or below having at least about 80 % amino acid sequence identity with a full-length native sequence Bolekine polypeptide sequence as disclosed herein, a Bolekine polypeptide sequence lacking the signal peptide as disclosed herein, an extracellular domain of a Bolekine polypeptide, with or without the signal peptide, as disclosed herein or any other fragment of a full-length Bolekine polypeptide sequence as disclosed herein. Such Bolekine polypeptide variants include, for instance, Bolekine polypeptides wherein one or more amino acid residues are added, or deleted, at the N- or C-terminus of the full-length native amino acid sequence. Ordinarily, a Bolekine polypeptide variant will have at least about 80% amino acid sequence identity, alternatively at least about 81 % amino acid sequence identity, alternatively at least about 82% amino acid sequence identity, alternatively at least about 83% amino acid sequence identity, alternatively at least about 84% amino acid sequence identity, alternatively at least about 85% amino acid sequence identity, alternatively at least about 86% amino acid sequence identity, alternatively at least about 87 % amino acid sequence identity, alternatively at least about 88 % amino acid sequence identity, alternatively at least about 89% amino acid sequence identity, alternatively at least about 90% amino acid sequence identity, alternatively at least about 91% amino acid sequence identity, alternatively at least about 92% amino acid sequence identity, alternatively at least about 93% amino acid sequence identity, alternatively at least about 94 % amino acid sequence identity, alternatively at least about 95 % amino acid sequence identity, alternatively at least about 96 % amino acid sequence identity, alternatively at least about 97% amino acid sequence identity, alternatively at least about 98% amino acid sequence identity and alternatively at least about 99% amino acid sequence identity to a full-length native sequence Bolekine polypeptide sequence as disclosed herein, a Bolekine polypeptide sequence lacking the signal peptide as disclosed herein, an extracellular domain of a Bolekine polypeptide, with or without the signal peptide, as disclosed herein or any other specifically defined fragment of a full-length Bolekine polypeptide sequence as disclosed herein. Ordinarily, Bolekine variant polypeptides are at least about 10 amino acids in length, alternatively at least about 20 amino acids in length, alternatively at least about 30 amino acids in length, alternatively at least about 40 amino acids in length, alternatively at least about 50 amino acids in length, alternatively at least about 60 amino acids in length, alternatively at least about 70 amino acids in length, alternatively at least about 80 amino acids in length, alternatively at least about 90 amino acids in length, alternatively at least about 100 amino acids in length, alternatively at least about 150 amino acids in length, alternatively at least about 200 amino acids in length, alternatively at least about 300 amino acids in length, or more. "Percent (%) amino acid sequence identity" with respect to the Bolekine polypeptide sequences identified herein is defined as the percentage of amino acid residues in a candidate sequence that are identical with the amino acid residues in the specific Bolekine polypeptide sequence, after aligning the sequences and introducing gaps, if necessary, to achieve the maximum percent sequence identity, and not considering any conservative substitutions as part of the sequence identity. Alignment for purposes of determining percent amino acid sequence identity can be achieved in various ways that are within the skill in the art, for instance, using publicly available computer software such as BLAST, BLAST-2, ALIGN or Megalign (DNASTAR) software. Those skilled in the art can determine appropriate parameters for measuring alignment, including any algorithms needed to achieve maximal alignment over the full length of the sequences being compared. For purposes herein, however, % amino acid sequence identity values are generated using the sequence comparison computer program ALIGN-2, wherein the complete source code for the ALIGN-2 program is provided in Table 1 below. The ALIGN-2 sequence comparison computer program was authored by Genentech, Inc. and the source code shownin Table 1 below has been filed with user documentation in the U.S. Copyright Office, Washington D.C., 20559, where it is registered under U.S. Copyright Registration No. TXU510087. The ALIGN-2 program is publicly available through Genentech, Inc. , South San Francisco, California or may be compiled from the source code provided in Table 1 below. The ALIGN-2 program should be compiled for use on a UNIX operating system, preferably digital UNIX V4.0D . All sequence comparison parameters are set by the ALIGN-2 program and do not vary. In situations where ALIGN-2 is employed for amino acid sequence comparisons, the % amino acid sequence identity of a given amino acid sequence A to, with, or against a given amino acid sequence B (which can alternatively be phrased as a given amino acid sequence A that has or comprises a certain % amino acid sequence identity to, with, or against a given amino acid sequence B) is calculated as follows: 100 times the fraction X/Y where X is the number of amino acid residues scored as identical matches by the sequence alignment program ALIGN-2 in that program's alignment of A and B, and where Y is the total number of amino acid residues in B. It will be appreciated that where the length of amino acid sequence A is not equal to the length of amino acid sequence B, the % amino acid sequence identity of A to B will not equal the % amino acid sequence identity of B to A. As examples of % amino acid sequence identity calculations using this method, Tables 2 and 3 demonstrate how to calculate the % amino acid sequence identity of the amino acid sequence designated "Comparison Protein" to the amino acid sequence designated "Bolekine", wherein "Bolekine" represents the amino acid sequence of a hypothetical Bolekine polypeptide of interest, "Comparison Protein" represents the amino acid sequence of a polypeptide against which the "Bolekine" polypeptide of interest is being compared, and "X, "Y" and "Z" each represent different hypothetical amino acid residues. Unless specifically stated otherwise, all % amino acid sequence identity values used herein are obtained as described in the immediately preceding paragraph using the ALIGN-2 computer program. However, % amino acid sequence identity values may also be obtained as described below by using the WU-BLAST-2 computer program (Altschul et al., Methods in Enzvmology 266:460-480 (1996)). Most of the WU-BLAST-2 search parameters are set to the default values. Those not set to default values, i.e. , the adjustable parameters, are set with the following values: overlap span = 1, overlap fraction = 0.125, word threshold (T) = 11, and scoring matrix = BLOSUM62. When WU-BLAST-2 is employed, a % amino acid sequence identity value is determined by dividing (a) the number of matching identical amino acid residues between the amino acid sequence of the Bolekine polypeptide of interest having a sequence derived from the native Bolekine polypeptide and the comparison amino acid sequence of interest (i.e., the sequence against which the Bolekine polypeptide of interest is being compared which may be a Bolekine variant polypeptide) as determined by WU-BLAST-2 by (b) the total number of amino acid residues of the Bolekine polypeptide of interest. For example, in the statement "a polypeptide comprising an the amino acid sequence A which has or having at least 80% amino acid sequence identity to the amino acid sequence B", the amino acid sequence A is the comparison amino acid sequence of interest and the amino acid sequence B is the amino acid sequence of the Bolekine polypeptide of interest. Percent amino acid sequence identity may also be determined using the sequence comparison program NCBI-BLAST2 (Altschul et al., Nucleic Acids Res. 25:3389-3402 (1997)). The NCBI-BLAST2 sequence comparison program may be downloaded from http://www.ncbi.nlm.nih.gov or otherwise obtained from the National Institute of Health, Bethesda, MD . NCBI-BLAST2 uses several search parameters , wherein all of those search parameters are set to default values including, for example, unmask = yes, strand = all, expected occurrences = 10, minimum low complexity length = 15/5, multi-pass e-value = 0.01, constant for multi-pass = 25, dropoff for final gapped alignment = 25 and scoring matrix = BLOSUM62. In situations where NCBI-BLAST2 is employed for amino acid sequence comparisons, the % amino acid sequence identity of a given amino acid sequence A to, with, or against a given amino acid sequence B (which can alternatively be phrased as a given amino acid sequence A that has or comprises a certain % amino acid sequence identity to, with, or against a given amino acid sequence B) is calculated as follows: 100 times the fraction X/Y where X is the number of amino acid residues scored as identical matches by the sequence alignment program NCBI-BLAST2 in that program's alignment of A and B , and where Y is the total number of amino acid residues in B. It will be appreciated that where the length of amino acid sequence A is not equal to the length of amino acid sequence B, the % amino acid sequence identity of A to B will not equal the % amino acid sequence identity of B to A. "Bolekine variant polynucleotide" or "Bolekine variant nucleic acid sequence" means a nucleic acid molecule which encodes an active Bolekine polypeptide as defined below and which has at least about 80% nucleic acid sequence identity with a nucleotide acid sequence encoding a full-length native sequence Bolekine polypeptide sequence as disclosed herein, a full-length native sequence Bolekine polypeptide sequence lacking the signal peptide as disclosed herein, an extracellular domain of a Bolekine polypeptide, with or without the signal peptide, as disclosed herein or any other fragment of a full-length Bolekine polypeptide sequence as disclosed herein. Ordinarily, a Bolekine variant polynucleotide will have at least about 80% nucleic acid sequence identity, alternatively at least about 81 % nucleic acid sequence identity, alternatively at least about 82 % nucleic acid sequence identity, alternatively at least about 83 % nucleic acid sequence identity, alternatively at least about 84% nucleic acid sequence identity, alternatively at least about 85% nucleic acid sequence identity, alternatively at least about 86% nucleic acid sequence identity, alternatively at least about 87% nucleic acid sequence identity, alternatively at least about 88 % nucleic acid sequence identity, alternatively at least about 89 % nucleic acid sequence identity, alternatively at least about 90% nucleic acid sequence identity, alternatively at least about 91 % nucleic acid sequence identity, alternatively at least about 92% nucleic acid sequence identity, alternatively at least about 93% nucleic acid sequence identity, alternatively at least about 94% nucleic acid sequence identity, alternatively at least about 95% nucleic acid sequence identity, alternatively at least about 96% nucleic acid sequence identity, alternatively at least about 97% nucleic acid sequence identity, alternatively at least about 98% nucleic acid sequence identity and alternatively at least about 99% nucleic acid sequence identity with a nucleic acid sequence encoding a full-length native sequence Bolekine polypeptide sequence as disclosed herein, a full-length native sequence Bolekine polypeptide sequence lacking the signal peptide as disclosed herein, an extracellular domain of a Bolekine polypeptide, with or without the signal sequence, as disclosed herein or any other fragment of a full-length Bolekine polypeptide sequence as disclosed herein. Variants do not encompass the native nucleotide sequence. Ordinarily, Bolekine variant polynucleotides are at least about 30 nucleotides in length, alternatively at least about 60 nucleotides in length, alternatively at least about 90 nucleotides in length, alternatively at least about 120 nucleotides in length, alternatively at least about 150 nucleotides in length, alternatively at least about 180 nucleotides in length, alternatively at least about 210 nucleotides in length, alternatively at least about 240 nucleotides in length, alternatively at least about 270 nucleotides in length, alternatively at least about 300 nucleotides in length, alternatively at least about 450 nucleotides in length, alternatively at least about 600 nucleotides in length, alternatively at least about 900 nucleotides in length, or more. "Percent (%) nucleic acid sequence identity" with respect to Bolekine-encoding nucleic acid sequences identified herein is defined as the percentage of nucleotides in a candidate sequence that are identical with the nucleotides in the Bolekine nucleic acid sequence of interest, after aligning the sequences and introducing gaps, if necessary, to achieve the maximum percent sequence identity. Alignment for purposes of determining percent nucleic acid sequence identity can be achieved in various ways that are within the skill in the art, for instance, using publicly available computer software such as BLAST, BLAST-2, ALIGN or Megalign (DNASTAR) software. For purposes herein, however, % nucleic acid sequence identity values are generated using the sequence comparison computer program ALIGN-2, wherein the complete source code for the ALIGN-2 program is provided in Table 1 below. The ALIGN-2 sequence comparison computer program was authored by Genentech, Inc. and the source code shown in Table 1 below has been filed with user documentation in the U.S. Copyright Office, Washington D.C., 20559, where it is registered under U.S. Copyright Registration No. TXU510087. The ALIGN-2 program is publicly available through Genentech, Inc., South San Francisco, California or may be compiled from the source code provided in Table 1 below. The ALIGN-2 program should be compiled for use on a UNLX operating system, preferably digital UNLX V4.0D. All sequence comparison parameters are set by the ALIGN-2 program and do not vary. In situations where ALIGN-2 is employed for nucleic acid sequence comparisons, the % nucleic acid sequence identity of a given nucleic acid sequence C to, with, or against a given nucleic acid sequence D (which can alternatively be phrased as a given nucleic acid sequence C that has or comprises a certain % nucleic acid sequence identity to, with, or against a given nucleic acid sequence D) is calculated as follows: 100 times the fraction W/Z where W is the number of nucleotides scored as identical matches by the sequence alignment program ALIGN-2 in that program's alignment of C and D, and where Z is the total number of nucleotides in D. It will be appreciated that where the length of nucleic acid sequence C is not equal to the length of nucleic acid sequence D, the % nucleic acid sequence identity of C to D will not equal the % nucleic acid sequence identity of D to C. As examples of % nucleic acid sequence identity calculations, Tables 4 and 5, demonstrate how to calculate the % nucleic acid sequence identity of the nucleic acid sequence designated "Comparison DNA" to the nucleic acid sequence designated "Bolekine-DNA", wherein "Bolekine-DNA" represents a hypothetical Bolekine- encoding nucleic acid sequence of interest, "Comparison DNA" represents the nucleotide sequence of a nucleic acid molecule against which the "Bolekine-DNA" nucleic acid molecule of interest is being compared, and "N" , "L" and "V" each represent different hypothetical nucleotides. Unless specifically stated otherwise, all % nucleic acid sequence identity values used herein are obtained as described in the immediately preceding paragraph using the ALIGN-2 computer program. However, % nucleic acid sequence identity values may also be obtained as described below by using the WU-BLAST-2 computer program (Altschul et al. , Methods in Enzvmology 266:460-480 (1996)). Most of the WU-BLAST-2 search parameters are set to the default values. Those not set to default values, i.e., the adjustable parameters, are set with the following values: overlap span = 1, overlap fraction = 0.125, word threshold (T) = 11, and scoring matrix = BLOSUM62. When WU-BLAST-2 is employed, a % nucleic acid sequence identity value is determined by dividing (a) the number of matching identical nucleotides between the nucleic acid sequence of the Bolekine polypeptide-encoding nucleic acid molecule of interest having a sequence derived from the native sequence Bolekine polypeptide-encoding nucleic acid and the comparison nucleic acid molecule of interest (i.e., the sequence against which the Bolekine polypeptide-encoding nucleic acid molecule of interest is being compared which may be a variant Bolekine polynucleotide) as determined by WU-BLAST-2 by (b) the total number of nucleotides of the Bolekine polypeptide-encoding nucleic acid molecule of interest. For example, in the statement "an isolated nucleic acid molecule comprising a nucleic acid sequence A which has or having at least 80% nucleic acid sequence identity to the nucleic acid sequence B", the nucleic acid sequence A is the comparison nucleic acid molecule of interest and the nucleic acid sequence B is the nucleic acid sequence of the Bolekine polypeptide-encoding nucleic acid molecule of interest. Percent nucleic acid sequence identity may also be determined using the sequence comparison program NCBI-BLAST2 (Altschul et al., Nucleic Acids Res. 25:3389-3402 (1997)). The NCBI-BLAST2 sequence comparison program may be downloaded from http://www.ncbi.nlm.nih.gov or otherwise obtained from the National Institute of Health, Bethesda, MD. NCBI-BLAST2 uses several search parameters, wherein all of those search parameters are set to default values including, for example, unmask = yes, strand = all, expected occurrences = 10, minimum low complexity length = 15/5, multi-pass e-value = 0.01, constant for multi-pass = 25, dropoff for final gapped alignment = 25 and scoring matrix = BLOSUM62. In situations where NCBI-BLAST2 is employed for sequence comparisons, the % nucleic acid sequence identity of a given nucleic acid sequence C to, with, or against a given nucleic acid sequence D (which can alternatively be phrased as a given nucleic acid sequence C that has or comprises a certain % nucleic acid sequence identity to, with, or against a given nucleic acid sequence D) is calculated as follows: 100 times the fraction W/Z where W is the number of nucleotides scored as identical matches by the sequence alignment program NCBI- BLAST2 in that program's alignment of C and D, and where Z is the total number of nucleotides in D. It will be appreciated that where the length of nucleic acid sequence C is not equal to the length of nucleic acid sequence D, the % nucleic acid sequence identity of C to D will not equal the % nucleic acid sequence identity of D to C. In other embodiments, Bolekine variant polynucleotides are nucleic acid molecules that encode an active Bolekine polypeptide and which are capable of hybridizing, preferably under stringent hybridization and wash conditions, to nucleotide sequences encoding a full-length Bolekine polypeptide as disclosed herein. Bolekine variant polypeptides may be those that are encoded by a Bolekine variant polynucleotide. "Isolated, " when used to describe the various polypeptides disclosed herein, means polypeptide that has been identified and separated and/or recovered from a component of its natural environment. Contaminant components of its natural environment are materials that would typically interfere with diagnostic or therapeutic uses for the polypeptide, and may include enzymes, hormones, and other proteinaceous or non-proteinaceous solutes. In preferred embodiments, the polypeptide will be purified (1) to a degree sufficient to obtain at least 15 residues of N-terminal or internal amino acid sequence by use of a spinning cup sequenator, or (2) to homogeneity by SDS-PAGE under non-reducing or reducing conditions using Coomassie blue or, preferably, silver stain. Isolated polypeptide includes polypeptide in situ within recombinant cells, since at least one component of the Bolekine polypeptide natural environment will not be present. Ordinarily, however, isolated polypeptide will be prepared by at least one purification step. An "isolated" Bolekine polypeptide-encoding nucleic acid or other polypeptide-encoding nucleic acid is a nucleic acid molecule that is identified and separated from at least one contaminant nucleic acid molecule with which it is ordinarily associated in the natural source of the polypeptide-encoding nucleic acid. An isolated polypeptide-encoding nucleic acid molecule is other than in the form or setting in which it is found in nature. Isolated polypeptide-encoding nucleic acid molecules therefore are-distinguished from the specific polypeptide- encoding nucleic acid molecule as it exists in natural cells. However, an isolated polypeptide-encoding nucleic acid molecule includes polypeptide-encoding nucleic acid molecules contained in cells that ordinarily express the polypeptide where, for example, the nucleic acid molecule is in a chromosomal location different from that of natural cells. The term "control sequences" refers to DNA sequences necessary for the expression of an operably linked coding sequence in a particular host organism. The control sequences that are suitable for prokaryotes, for example, include a promoter, optionally an operator sequence, and a ribosome binding site. Eukaryotic cells are known to utilize promoters, polyadenylation signals, and enhancers. Nucleic acid is "operably linked" when it is placed into a functional relationship with another nucleic acid sequence. For example, DNA for a presequence or secretory leader is operably linked to DNA for a polypeptide if it is expressed as a preprotein that participates in the secretion of the polypeptide; a promoter or enhancer is operably linked to a coding sequence if it affects the transcription of the sequence; or a ribosome binding site is operably linked to a coding sequence if it is positioned so as to facilitate translation. Generally, "operably linked" means that the DNA sequences being linked are contiguous, and, in the case of a secretory leader, contiguous and in reading phase. However, enhancers do not have to be contiguous. Linking is accomplished by ligation at convenient restriction sites. If such sites do not exist, the synthetic oligonucleotide adaptors or linkers are used in accordance with conventional practice. The term "antibody" is used in the broadest sense and specifically covers, for example, single anti- Bolekine monoclonal antibodies (including agonist, antagonist, and neutralizing antibodies), anti-Bolekine antibody compositions withpolyepitopic specificity, single chain anti-Bolekine antibodies, and fragments of anti- Bolekine antibodies (see below). The term "monoclonal antibody" as used herein refers to an antibody obtained from a population of substantially homogeneous antibodies, i.e., the individual antibodies comprising the population are identical except for possible naturally-occurring mutations that may be present in minor amounts. "Stringency" of hybridization reactions is readily determinable by one of ordinary skill in the art, and generally is an empirical calculation dependent upon probe length, washing temperature, and salt concentration. In general, longer probes require higher temperatures for proper annealing, while shorter probes need lower temperatures. Hybridization generally depends on the ability of denatured DNA to reanneal when complementary strands are present in an environment below their melting temperature. The higher the degree of desired homology between the probe and hybridizable sequence, the higher the relative temperature which can be used. As a result, it follows that higher relative temperatures would tend to make the reaction conditions more stringent, while lower temperatures less so. For additional details and explanation of stringency of hybridization reactions, see Ausubel et al., Current Protocols in Molecular Biology. Wiley Interscience Publishers, (1995). "Stringent conditions" or "high stringency conditions", as defined herein, may be identified by those that: (1) employ low ionic strength and high temperature for washing, for example 0.015 M sodium chloride/0.0015 M sodium citrate/0.1% sodium dodecyl sulfate at 50°C; (2) employ during hybridization a denaturing agent, such as formamide, for example, 50% (v/v) formamide with 0.1 % bovine serum dbumin/0.1 % Ficoll/0.1 % poly vinylpyrrolidone/50mM sodium phosphate buffer at pH 6.5 with 750 mM sodium chloride, 75 mM sodium citrate at 42°C; or (3) employ 50% formamide, 5 x SSC (0.75 M NaCl, 0.075 M sodium citrate), 50 mM sodium phosphate (pH 6.8), 0.1% sodium pyrophosphate, 5 x Denhardt's solution, sonicated salmon sperm DNA (50 μg/ml), 0.1 % SOS, and 10% dextran sulfate at 42°C, with washes at 42°C in 0.2 x SSC (sodium chloride/sodium citrate) and 50% formamide at 55 °C, followed by a high-stringency wash consisting of 0.1 x SSC containing EDTA at 55 °C. "Moderately stringent conditions" may be identified as described by Sambrook et al., Molecular Cloning: A Laboratory Manual, New York: Cold Spring Harbor Press, 1989, and include the use of washing solution and hybridization conditions (e.g., temperature, ionic strength and %SDS) less stringent that those described above. An example of moderately stringent conditions is overnight incubation at 37°C in a solution comprising: 20% formamide, 5 x SSC (150 mM NaCl, 15 mM trisodium citrate), 50 mM sodium phosphate (pH 7.6), 5 x Denhardt's solution, 10% dextran sulfate, and 20 mg/ml denatured sheared salmon sperm DNA, followed by washing the filters in 1 x SSC at about 37-50°C. The skilled artisan will recognize how to adjust the temperature, ionic strength, etc. as necessary to accommodate factors such as probe length and the like. The term "epitope tagged" when used herein refers to a ehimeric polypeptide comprising a Bolekine polypeptide fused to a "tag polypeptide" . The tag polypeptide has enough residues to provide an epitope against which an antibody can be made, yet is short enough such that it does not interfere with activity of the polypeptide to which it is fused. The tag polypeptide preferably also is fairly unique so that the antibody does not substantially cross-react with other epitopes. Suitable tag polypeptides generally have at least six amino acid residues and usually between about 8 and 50 amino acid residues (preferably, between about 10 and 20 amino acid residues). As used herein, the term "immunoadhesin" designates antibody-like molecules which combine the binding specificity of a heterologous protein (an "adhesin") with the effector functions of immunoglobulin constant domains. Structurally, the immunoadhesins comprise a fusion of an amino acid sequence with the desired binding specificity which is other than the antigen recognition and binding site of an antibody (i.e., is "heterologous"), and an immunoglobulin constant domain sequence. The adhesin part of an immunoadhesin molecule typically is a contiguous amino acid sequence comprising at least the binding site of a receptor or a ligand. The immunoglobulin constant domain sequence in the immunoadhesin may be obtained from any immunoglobulin, such as IgG-1, IgG-2, IgG-3, or IgG-4 subtypes, IgA (including IgA-1 and IgA-2), IgE, IgD or IgM. "Active" or "activity" for the purposes herein refers to form(s) of a Bolekine polypeptide which retain a biological and/or an immunological activity of native or naturally-occurring Bolekine, wherein "biological" activity refers to a biological function (either inhibitory or stimulatory) caused by a native or naturally-occurring Bolekine other than the ability to induce the production of an antibody against an antigenic epitope possessed by a native or naturally-occurring Bolekine and an "immunological" activity refers to the ability to induce the production of an antibody against an antigenic epitope possessed by a native or naturally-occurring Bolekine. The term "antagonist" is used in the broadest sense, and includes any molecule that partially or fully blocks, inhibits, or neutralizes a biological activity of a native Bolekine polypeptide disclosed herein. In a similar manner, the term "agonist" is used in the broadest sense and includes any molecule that mimics a biological activity of a native Bolekine polypeptide disclosed herein. Suitable agonist or antagonist molecules specifically include agonist or antagonist antibodies or antibody fragments, fragments or amino acid sequence variants of native Bolekine polypeptides, peptides, antisense oligonucleotides, small organic molecules, etc. Methods for identifying agonists or antagonists of a Bolekine polypeptide may comprise contacting a Bolekine polypeptide with a candidate agonist or antagonist molecule and measuring a detectable change in one or more biological activities normally associated with the Bolekine polypeptide. "Treatment" refers to both therapeutic treatment and prophylactic or preventative measures, wherein the object is to prevent or slow down (lessen) the targeted pathologic condition or disorder. Those in need of treatment include those already with the disorder as well as those prone to have the disorder or those in whom the disorder is to be prevented. "Chronic" administration refers to administration of the agent(s) in a continuous mode as opposed to an acute mode, so as to maintain the initial therapeutic effect (activity) for an extended period of time. "Intermittent" administration is treatment that is not consecutively done without interruption, but rather is cyclic in nature. "Mammal" for purposes of treatment refers to any animal classified as a mammal, including humans, domestic and farm animals, and zoo, sports, or pet animals, such as dogs, cats, cattle, horses, sheep, pigs, goats, rabbits, etc. Preferably, the mammal is human. Administration "in combination with" one or more further therapeutic agents includes simultaneous (concurrent) and consecutive administration in any order. "Carriers" as used herein include pharmaceutically acceptable carriers, excipients, or stabilizers which are nontoxic to the cell or mammal being exposed thereto at the dosages and concentrations employed. Often the physiologically acceptable carrier is an aqueous pH buffered solution. Examples of physiologically acceptable carriers include buffers such as phosphate, citrate, and other organic acids; antioxidants including ascorbic acid; low molecular weight (less than about 10 residues) polypeptide; proteins, such as serum albumin, gelatin, or immunoglobulins; hydrophilic polymers such as polyvinylpyrrolidone; amino acids such as glycine, glutamine, asparagine, arginine or lysine; monosaccharides, disaccharides, and other carbohydrates including glucose, mannose, or dextrins; chelating agents such as EDTA; sugar alcohols such as mannitol or sorbitol; salt- forming counterions such as sodium; and/or nonionic surfactants such as TWEEN™, polyethylene glycol (PEG), and PLURONICS™. "Antibody fragments" comprise a portion of an intact antibody, preferably the antigen binding or variable region of the intact antibody. Examples of antibody fragments include Fab, Fab', F(ab') 2 , and Fv fragments; diabodies; linear antibodies (Zapata et al., Protein Eng. 8(10): 1057-1062 [1995]); single-chain antibody molecules; and multispecific antibodies formed from antibody fragments. Papain digestion of antibodies produces two identical antigen-binding fragments, called "Fab" fragments, each with a single antigen-binding site, and a residual "Fc" fragment, a designation reflecting the ability to crystallize readily. Pepsin treatment yields an F(ab') 2 fragment that has two antigen-combining sites and is still capable of cross-linking antigen. "Fv" is the minimum antibody fragment which contains a complete antigen-recognition and -binding site. This region consists of a dimer of one heavy- and one light-chain variable domain in tight, non-covalent association. It is in this configuration that the three CDRs of each variable domain interact to define an antigen- binding site on the surface of the V H -V L dimer. Collectively, the six CDRs confer antigen-binding specificity to the antibody. However, even a single variable domain (or half of an Fv comprising only three CDRs specific for an antigen) has the ability to recognize and bind antigen, although at a lower affinity than the entire binding site. The Fab fragment also contains the constant domain of the light chain and the first constant domain (CHI) of the heavy chain. Fab fragments differ from Fab' fragments by the addition of a few residues at the carboxy terminus of the heavy chain CHI domain including one or more cysteines from the antibody hinge region. Fab ' -SH is the designation herein for Fab ' in which the cysteine residue(s) of the constant domains bear a free thiol group. F(ab') 2 antibody fragments originally were produced as pairs of Fab' fragments which have hinge cysteines between them. Other chemical couplings of antibody fragments are also known. The "light chains" of antibodies (immunoglobulins) from any vertebrate species can be assigned to one of two clearly distinct types, called kappa and lambda, based on the amino acid sequences of their constant domains. Depending on the amino acid sequence of the constant domain of their heavy chains, immunoglobulins can be assigned to different classes. There are five major classes of immunoglobulins: IgA, IgD, IgE, IgG, and IgM, and several of these may be further divided into subclasses (isotypes), e.g., IgGl, IgG2, IgG3, IgG4, IgA, and IgA2. "Single-chain Fv" or "sFv" antibody fragments comprise the V H and V L domains of antibody, wherein these domains are present in a single polypeptide chain. Preferably, the Fv polypeptide further comprises a polypeptide linker between the V H and V L domains which enables the sFv to form the desired structure for antigen binding. For a review of sFv, see Pluckthun in The Pharmacology of Monoclonal Antibodies, vol. 113, Rosenburg and Moore eds., Springer- Verlag, New York, pp. 269-315 (1994). The term "diabodies" refers to small antibody fragments with two antigen-binding sites, which fragments comprise a heavy-chain variable domain (V H ) connected to a light-chain variable domain (V L ) in the same polypeptide chain (V H -V L ). By using a linker that is too short to allow pairing between the two domains on the same chain, the domains are forced to pair with the complementary domains of another chain and create two antigen-binding sites. Diabodies are described more fully in, for example, EP 404,097; WO 93/11161 ; and Hollinger et al., Proc. Natl. Acad. Sci. USA. 90:6444-6448 (1993). An "isolated" antibody is one which has been identified and separated and/or recovered from a component of its natural environment. Contaminant components of its natural environment are materials which would interfere with diagnostic or therapeutic uses for the antibody, and may include enzymes, hormones, and other proteinaceous or nonproteinaceous solutes. In preferred embodiments, the antibody will be purified (1) to greater than 95 % by weight of antibody as determined by the Lowry method, and most preferably more than 99% by weight, (2) to a degree sufficient to obtain at least 15 residues of N-terminal or internal amino acid sequence by use of a spinning cup sequenator, or (3) to homogeneity by SDS-PAGE under reducing or nonreducing conditions using Coomassie blue or, preferably, silver stain. Isolated antibody includes the antibody in situ within recombinant cells since at least one component of the antibody's natural environment will not be present. Ordinarily, however, isolated antibody will be prepared by at least one purification step. An antibody that "specifically binds to" or is "specific for" a particular polypeptide or an epitope on a particular polypeptide is one that binds to that particular polypeptide or epitope on a particular polypeptide without substantially binding to any other polypeptide or polypeptide epitope. The word "label" when used herein refers to a detectable compound or composition which is conjugated directly or indirectly to the antibody so as to generate a "labeled" antibody. The label may be detectable by itself (e.g. radioisotope labels or fluorescent labels) or, in the case of an enzymatic label, may catalyze chemical alteration of a substrate compound or composition which is detectable. By "solid phase" is meant a non-aqueous matrix to which the antibody of the present invention can adhere. Examples of solid phases encompassed herein include those formed partially or entirely of glass (e.g. , controlled pore glass), polysaccharides (e.g., agarose), polyacrylamides, polystyrene, polyvinyl alcohol and silicones. In certain embodiments, depending on the context, the solid phase can comprise the well of an assay plate; in others it is a purification column (e.g., an affinity chromatography column). This term also includes a discontinuous solid phase of discrete particles, such as those described in U.S. Patent No. 4,275,149. A "liposome" is a small vesicle composed of various types of lipids, phospholipids and/or surfactant which is useful for delivery of a drug (such as a Bolekine polypeptide or antibody thereto) to a mammal. The components of the liposome are commonly arranged in a bilayer formation, similar to the lipid arrangement of biological membranes. A "small molecule" is defined herein to have a molecular weight below about 500 Daltons. An "effective amount" of a polypeptide disclosed herein or an agonist or antagonist thereof is an amount sufficient to carry out a specifically stated purpose. An "effective amount" may be determined empirically and in a routine manner, in relation to the stated purpose. A "pluripotent cell" is defined herein as a cell that is not fixed to a developmental lineage. Table 1 /* * * C-C increased from 12 to 15 * Z is average of EQ * B is average of ND * match with stop is _M; stop-stop = 0; J (joker) match = 0 */ #define _M -8 /* value of a match with a stop */ int day[26][26] = { /* A " B C D E F G H I J K L M N O P Q R S T U V W X Y Z*/ /*A*/ 2, 0,-2, 0, 0,-4, 1,-1,-1, 0,-1,-2,-1, 0,_M, 1, 0,-2, 1, 1, 0, 0,-6, 0,-3, 0}, /*B */ 0, 3,-4, 3, 2,-5, 0, 1,-2, 0, 0,-3,-2, 2,_ ,-1, 1, 0, 0, 0, 0,-2,-5, 0,-3, 1}, /*C*/ 2,-4,15,-5,-5,-4,-3,-3,-2, 0,-5,-6,-5,-4,_M,-3,-5,-4, 0,-2, 0,-2,-8, 0, 0,-5}, /*D*/ 0, 3,-5, 4, 3,-6, 1, 1,-2, 0, 0,-4,-3, 2,_M,-1, 2,-1, 0, 0, 0,-2,-7, 0,-4, 2}, /*E*/ 0, 2,-5, 3, 4,-5, 0, 1,-2, 0, 0,-3,-2, 1,_M,-1, 2,-1, 0, 0, 0,-2,-7, 0,-4, 3}, /* p */ ■ 4,-5,-4,-6,-5, 9,-5,-2, 1, 0,-5, 2, 0,-4,_M,-5,-5,-4,-3,-3, 0,-1, 0, 0, 7,-5}, /*G*/ 1, 0,-3, 1, 0,-5, 5,-2,-3, 0,-2,-4,-3, 0,_M,-l,-l,-3, 1, 0, 0,-1,-7, 0,-5, 0}, /* H */ ■ 1, 1,-3, 1, 1,-2,-2, 6,-2, 0, 0,-2,-2, 2,_M, 0, 3, 2,-1,-1, 0,-2,-3, 0, 0, 2}, /* I */ -1,-2,-2,-2,-2, 1,-3,-2, 5, 0,-2, 2, 2,-2,_M,-2,-2,-2,-l, 0, 0, 4,-5, 0,-1,-2}, 1*1*1 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0,_M, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0}, /*K*/ •1, 0,-5, 0, 0,-5,-2, 0,-2, 0, 5,-3, 0, 1,_M,-1, 1, 3, 0, 0, 0,-2,-3, 0,-4, 0}, /*L*/ 2,-3,-6,-4,-3, 2,-4,-2, 2, 0,-3, 6, 4,-3,_M,-3,-2,-3,-3,-l, 0, 2,-2, 0,-1,-2}, /*M*/ ■ 1,-2,-5,-3,-2, 0,-3,-2, 2, 0, 0, 4, 6,-2,_M,-2,-l, 0,-2,-1, 0, 2,-4, 0,-2,-1}, /*N*/ 0, 2,-4, 2; 1,-4, 0, 2,-2, 0, 1,-3,-2, 2,_M,-1, 1, 0, 1, 0, 0,-2,-4, 0,-2, 1}, /*0*/ M,_M,_M,_M,_M,_M,_M,_M,_M,_M,_M,_M,_M,_M, 0,_M,_M,_M,_M,_M,_M,_M,_M,_M,_M,_M}, /* p */ 1,-1 -3,-1,-1,-5,-1, 0,-2, 0,-l,-3,-2,-l,_M, 6, 0, 0, 1, 0, 0,-1,-6, 0,-5, 0}, /*Q*/ 0, 1 -5, 2, 2,-5,-1, 3,-2, 0, 1,-2,-1, 1,_M, 0, 4, 1,-1,-1, 0,-2,-5, 0,-4, 3}, /*R*/ ■ 2,0 -4,-1,-1,-4,-3, 2,-2, 0, 3,-3, 0, 0,_M, 0, 1, 6, 0,-1, 0,-2, 2, 0,-4, 0}, /*S*/ 1,0 0, 0, 0,-3, 1,-1,-1, 0, 0,-3,-2, 1,_M, 1,-1, 0, 2, 1, 0,-1,-2, 0,-3, 0}, /* T */ 1,0 -2, 0, 0,-3, 0,-1, 0, 0, 0,-1,-1, 0,_M, 0,-1,-1, 1, 3, 0, 0,-5, 0,-3, 0}, /*u*/ 0,0 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0,_M, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0}, /* v */ 0,-2 -2,-2,-2,-1,-1,-2, 4, 0,-2, 2, 2,-2,_M,-l,-2,-2,-l, 0, 0, 4,-6, 0,-2,-2}, /*w*/ ■6,-5 -8,-7,-7, 0,-7,-3,-5, 0,-3,-2,-4,-4,_M,-6,-5, 2,-2,-5, 0,-6,17, 0, 0,-6}, t*X*f 0,0 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0,_M, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0}, /* Y */ ■3,-3 0,-4,-4, 7,-5, 0,-1, 0,-4,-l,-2,-2,_M,-5,-4,-4,-3,-3, 0,-2, 0, 0,10,-4}, 0, 1 -5, 2, 3,-5, 0, 2,-2, 0, 0,-2,-1, 1,_M, 0, 3, 0, 0, 0, 0,-2,-6, 0,-4, 4} }; Table 1 (conf) /* */ ^include <stdio.h> ^include <ctype.h> Mefine MAXJMP 16 /* max jumps in a diag */ Mefine MAXGAP 24 /* don't continue to penalize gaps larger than this */ Mefine JMPS 1024 /* max jmps in an path */ Mefine MX 4 /* save if there's at least MX-1 bases since last jmp */ Mefine DMAT 3 /* value of matching bases */ Mefine DMIS 0 /* penalty for mismatched bases */ Mefine DINSO /* penalty for a gap */ Mefine DINSl /* penalty per base */ Mefine PINSO /* penalty for a gap */ Mefine PINSl /* penalty per residue */ struct jmp { short nfMAXJMP]; /* size of jmp (neg for dely) */ unsigned short x[MAXJMP]; /* base no. of jmp in seq x */ }; /* limits seq to 2 Λ 16 -1 */ struct diag { int score; /* score at last jmp */ long offset; /* offset of prev block */ short ijmp; /* current jmp index */ struct jmp jp; I* list of jmps */ }; struct path { int spc; /* number of leading spaces */ short n[JMPS];/* size of jmp (gap) */ int x[JMPS];/* loc of jmp (last elem before gap) */ }; char *ofιle; /* output file name */ char *namex[2]; /* seq names: getseqs() */ char *prog; /* prog name for err msgs */ char *seqx[2]; /* seqs: getseqs() */ int dmax; /* best diag: nw() */ int dmaxO; /* final diag */ int dna; /* set if dna: main() */ int endgaps; /* set if penalizing end gaps */ int gapx, gapy; /* total gaps in seqs */ int lenO, lenl; /* seq lens */ int ngapx, πgapy; /* total size of gaps */ int smax; /* max score: nw() */ int *xbm; /* bitmap for matching */ long offset; /* current offset in jmp file */ struct diag *dx; /* holds diagonals */ struct path pp[2]; /* holds path for seqs */ char *calloc(), *malloc(), *index(), *strcpy(); char *getseq(), *g_calloc(); Table 1 (cont*) /* Needleman-Wunsch alignment program * * usage: progs filel file2 * where filel and file2 are two dna or two protein sequences. * The sequences can be in upper- or lower-case an may contain ambiguity * Any lines beginning with '; ', ' > ' or ' < ' are ignored * Max file length is 65535 (limited by unsigned short x in the jmp struct) * A sequence with 1/3 or more of its elements ACGTU is assumed to be DNA * Output is in the file "align.out" * The program may create a tmp file in /tmp to hold info about traceback. * Original version developed under BSD 4.3 on a vax 8650 */ #include "nw.h" #include "day.h" static _dbval[26] = { 1,14,2,13,0,0,4,11,0,0,12,0,3,15,0,0,0,5,6,8,8,7,9,0,10,0 >; static jpbval[26] = { 1, 2|(1< <('D'-'A'))|(1< <('N'-'A')), 4, 8, 16, 32, 64, 128, 256, OxFFFFFFF, 1< < 10, 1< < 11, 1< < 12, 1< < 13, 1< < 14, 1<<15, 1<<16, 1<<17, 1<<18, 1<<19, 1< <20, 1< <21, 1< <22, 1<<23, 1<<24, 1<<25|(1<<('E'-'A'))|(1<<('Q'-'A')) }; int ac; char *avQ; { prog = av[0]; if(ac!=3){ fprintf(stderr, "usage: %s filel fιle2\n", prog); fprintf(stderr, "where filel and file2 are two dna or two protein sequences. \n"); fρriπtf(stderr, "The sequences can be in upper- or lower-case\n"); fprintf(stderr,"Any lines beginning with ';' or ' < ' are ignored\n"); fprintf(stderr, "Output is in the file \"align.out\"\n"); exit(l); } namex[0] = av[l]; namex[l] = av[2]; seqx[0] = getseq(namex[0], &len0); seqx[l] = getseq(namex[l], &lenl); xbm = (dna)? _dbval : _pbval; endgaps = 0; /* 1 to penalize endgaps */ ofile = "align.out"; /* output file */ nw(); /* fill in the matrix, get the possible jmps */ readjmpsO; /* get the actual jmps */ print(); /* print stats, alignment */ cleanup(0); /* unlink any tmp files */ Table 1 (conf /* do the alignment, return best score: main() * dna: values in Fitch and Smith, PNAS, 80, 1382-1386, 1983 * pro: PAM 250 values * When scores are equal, we prefer mismatches to any gap, prefer * a new gap to extending an ongoing gap, and prefer a gap in seqx * to a gap in seq y. nw() n { char *px, *py; /* seqs and ptrs */ int *ndely, *dely; /* keep track of dely */ it ndelx, delx; /* keep track of delx */ int *tmp; /* for swapping rowO, rowl */ int mis; /* score for each type */ int insO, insl; /* insertion penalties */ register id; /* diagonal index */ register ii; /* jmp index */ register *col0, *coll; /* score for curr, last row */ register xx, yy; /* index into seqs */ dx = (struct diag *)g_calloc("to get diags", lenO+lenl + l, sizeof(struct diag)); ■ ndely = (int *)g_calloc("to get ndely", lenl + 1, sizeof(int)); dely = (int *)g_calloc("to get dely", lenl + 1, sizeof(int)); colO = (int *)g_calloc("to get colO", lenl + 1, sizeof(int)); coll = (int *)g_calloc("to get coll", lenl + 1, sizeof(int)); insO = (dna)? DINSO : PINSO; insl = (dna)? DINSl : PINSl; smax = -10000; if (endgaps) { for (co!0[0] = dely[0] = -insO, yy = 1; yy < = lenl; yy+ +) { col0[yy] = delyfyy] = col0[yy-l] - insl; ndely[yy] = yy; } col0[0] = 0; /* Waterman Bull Math Biol 84 */ } else for (yy = 1; yy < = lenl; yy+ +) delyfyy] = -insO; /* fill in match matrix */ for (px = seqx[0], xx = 1; xx < = lenO; px+ + , xx+ +) { /* initialize first entry in col */ if (endgaps) { if (xx = = 1) coll[0] = delx = -(insO+insl); else coll[0] = delx = col0[0] - insl; ndelx = xx; } else { coll[0] = 0; delx = -insO; ndelx = 0; Table 1 (conf ...nw seqx[l], yy = 1; yy < = lenl; py+ + , yy+ +) { mis = col0[yy-l]; if (dna) mis + = (xbm[*px-' A']&xbm[*py-'A'])? DMAT : DMIS; else mis + = layp f rpx-'A'Jppy-'A']; /* update penalty for del in x seq; * favor new del over ongong del * ignore MAXGAP if weighting endgaps */ if (endgaps 1 1 ndelyfyy] < MAXGAP) { if (coIOfyy] - insO > = delyfyy]) { dely[yy] = col0[yy] - (insO+insl); ndelyfyy] = 1; } else { delyfyy] -= insl; ndely[yy] + + ; } } else { if (coIOfyy] - (insO+insl) > = delyfyy]) { delyfyy] = coIOfyy] - (insO+insl); ndelyfyy] = 1; } else ndelyfyy] + +; } /* update penalty for del in y seq; * favor new del over ongong del */ if (endgaps 1 1 ndelx < MAXGAP) { if (coll[yy-l] - insO > = delx) { delx = coll[yy-l] - (insO+insl); ndelx = 1; } else { delx -= insl; ndelx+ + ; } else { if (coll[yy-l] - (insO+insl) > = delx) { delx = coll[yy-l] - (insO+insl); ndelx = 1; } else ndelx+ + ; } /* pick the maximum score; we're favoring * mis over any del and delx over dely */ Table 1 (conf) ...nw id = xx - yy + lenl - 1; if (mis > = delx && mis > = delyfyy]) collfyy] = mis; else if (delx > = delyfyy]) { collfyy] = delx; ij = dxfid]. ijmp; if (dx[id].jp.n[0] && (!dna 1 1 (ndelx > = MAXJMP && xx > dxfid] jp.xfij] +MX) | ] mis > dxfid]. score + DINSO)) { dxfid]. ijmp+ + ; if (++ij > = MAXJMP) { writejmps(id); ij = dxfid]. ijmp = 0; dxfid]. offset = offset; offset + = sizeof (struct jmp) + sizeof (offset); } dx[id].jp.n[ij] = ndelx; dxfid] .jp.xfij] = xx; dxfid]. score = delx; } else { collfyy] = delyfyy]; ij = dxfid]. ijmp; if (dxfid] Jp.nfO] && (!dna 1 1 (ndelyfyy] > = MAXJMP && xx > dxfid] jp.x[ij]+MX) 1 1 mis > dxfid]. score+DINSO)) { dxfid]. ijmp+ + ; if (+ +ij > = MAXJMP) { writejmps(id); ij = dxfid]. ijmp = 0; dxfid]. offset = offset; offset + = sizeof (struct jmp) + sizeof (offset); } } dxfid] .jp.nfij] = -ndelyfyy]; dxfid] .jp.xfij] = xx; dxfid]. score = delyfyy]; } if (xx = = lenO && yy < lenl) { /* last col */ if (endgaps) collfyy] -= ins0+insl*(lenl-yy); if (collfyy] > smax) { smax = collfyy]; dmax = id; } } } if (endgaps && xx < lenO) coll[yy-l] -= ins0+insl*(len0-xx); if (coll[yy-l] > smax) { smax = coll[yy-l]; dmax = id; } tmp = colO; colO = coll; coll = tmp; } (void) free((char *)ndely); (void) free((char *)dely); (void) free((char *)col0) (void) free((char *)coll) Table 1 (conf) /* * * print() — only routine visible outside this module * * static: * getmat() — trace back best path, count matches: print() * pr_align() — print alignment of described in array pQ: print() * dumpblockO — dump a block of lines with numbers, stars: pr_align() * nums() — put out a number line: dumpblockO * putline() — put out a line (name, [num], seq, [num.]): dumpblockO * starsO - -put a line of stars: dumpblockO * stripname() — strip any path and prefix from a seqname */ include "nw.h" Mefine SPC 3 Mefine P_LINE 256 /* maximum output line */ Mefine P SPC 3 /* space between name or num and seq */ extern day [26] [26]; int olen; /* set output line length */ FILE *fe; /* output file */ printo print { int lx, ly, firstgap, lastgap; /* overlap */ if ((fx = fopen(ofile, "w")) = = 0) { fprintf(stderr,"%s: can't write %s\n", prog, ofile); cleanup(l); } iprintf(fx, " < first sequence: %s (length = %d)\n", namexfO], lenO); fprintf(fx, " < second sequence: %s (length = %d)\n", namex[l], lenl); olen = 60; lx = lenO; ly = lenl; firstgap = lastgap = 0; if (dmax < lenl - 1) { /* leading gap in x */ pp[0].spc = firstgap = lenl - dmax - 1; ly -= pp[0].spc; } else if (dmax > lenl - 1) { /* leading gap in y */ pp[l].spc = Firstgap = dmax - (lenl - 1); lx -= pp[l].spc; } if (dmaxO < lenO - 1) { /* trailing gap in x */ lastgap = lenO - dmaxO -1; ]χ -= lastgap; } else if (dmaxO > lenO - 1) { /* trailing gap in y */ lastgap = dmaxO - (lenO - 1); ly -= lastgap; getmatflx, ly, firstgap, lastgap); pr_align(); Table 1 (conf) /* * trace back the best path, count matches */ static getmat(lx, ly, firstgap, lastgap) getmat int lx, ly; /* "core" (minus endgaps) */ int firstgap, lastgap; /* leading trailing overlap */ { int nm, iO, il, sizO, sizl; char outx[32]; double pet; register nO, nl; register char *p0, *pl; /* get total matches, score */ iO = il = sizO = sizl = 0; pO = seqx[0] + pp[l].spc; pi = seqx[l] + pp[0].spc; nO = pp[l].spc + 1; nl = pp[0].spc + 1; nm = 0; while ( *p0 && *pl ) { if (sizO) { pi++; nl + + ; sizO--; } else if (sizl) { p0+ + ; n0+ + ; sizl-; } else { if (xbm[*pO-'A']&xbm[*pl-'A']) nm+ + ; if (n0+ + == pp[0].x[iO]) sizO = pp[0].n[iO+ +]; if (nl + + == pp[l].x[il]) sizl = pp[l].n[il + +]; p0+ +; pl + +; } } /* pet homology: * if penalizing endgaps, base is the shorter seq * else, knock off overhangs and take shorter core */ if (endgaps) lx = (lenO < lenl)? lenO : lenl; else lx = (lx < ly)? lx : ly; pet = 100.*(double)nm/(double)lx; fprintf(fx, "\n"); fprintf(fx, " < %d match%s in an overlap of %d: %.2f percent similarity\n", nm, (nm = = 1)? "" : "es", lx, pet); Table 1 (conf) fprintf(fx, " < gaps in First sequence: %d", gapx); .getmat if (gapx) { (void) sprintf(outx, " (%d %s%s)", ngapx, (dna)? "base": "residue", (ngapx == = 1)? "":"s"); f rintf(fx,"%s", outx); iprintf(fx, ", gaps in second sequence: d", gapy); if (gapy) { (void) sprintf(outx, " (%d %s%s)", ngapy, (dna)? "base": "residue", (ngapy = = 1)? "":"s"); fprintf(fx,"%s", outx); } if (dna) fprintf(fx, "\n< score: %d (match = %d, mismatch = %d, gap penalty = %d + %d per base)\n" smax, DMAT, DMIS, DINSO, DINSl); else fprintf(fx, "\n< score: %d (Dayhoff PAM 250 matrix, gap penalty = %d + %d per residue)\n", smax, PINSO, PINSl); if (endgaps) fprintf(fx, " < endgaps penalized, left endgap: %d %s%s, right endgap: %d %s%s\n", firstgap, (dna)? "base" : "residue", (firstgap == 1)? "" : "s", lastgap, (dna)? "base" : "residue", (lastgap = = 1)? "" : "s"); else fprintf(fx, " < endgaps not penalized\n"); static nm; /* matches in core — for checking */ static lmax; /* lengths of stripped file names */ static ij[2]; /* jmp index for a path */ static nc[2]; /* number at start of current line */ static ni[2]; /* current elem number — for gapping */ static siz[2]; static char *ps[2]; /* ptr to current element */ static char *po[2]; /* ptr to next output char slot */ static char oouutt[[22]][[IP_LINE]; /* output line */ static char starfP ] ϊ]; /* set by stars() */ /* * print alignment of described in struct path ppQ */ static pr_align() pr align { int nn; /* char count */ int more; register i; for (i = 0, lmax = 0; i < 2; i+ +) { nn = stripname(namex[i]); if (nn > lmax) lmax = nn; ncfi] = 1; nifi] = 1; sizfi] = ijfi] = 0; ps[i] = seqxfi]; po[i] = outffl; Table 1 (conf) for (nn = nm = 0, more = 1; more; ) { ...pr_align for (i = more = 0; i < 2; i+ +) { /* * do we have more of this sequence? */ if (!*ps[i]) continue; more+ +; if (pp[i].spc) { /* leading space */ *po[i] + + = ' '; pp[i].spc~; } else if (sizfi]) { /* in a gap */ *po[i] + + = '-'; sizfi]-; } else { /* we're putting a seq element */ *po[i] = *ps[i]; if (islower(*ps[i])) *ps[i] = toupper(*ps[i]); po[i] + + ; ps[i]+ +; /* * are we at next gap for this seq? */ if (ni[i] = = pp[i].x[ij[i]]) { /* * we need to merge all gaps * at this location */ sizfi] = pp[i].n[ij[i] + +]; while (nifi] == pp[i].x[ij[i]]) sizfi] += pp[i].n[ij[i] + +]; } ni[i] + + ; } } if (+ +nn = = olen 1 1 Imore && nn) { dumpblockO; for (i = 0; i < 2; i+ +) pofi] = outfi]; nn = 0; } } } /* * dump a block of lines, including numbers, stars: pr_align() */ static dumpblockO dumpblock { register i; for (i = 0; i < 2; i+ +) *po[i]~ = '\0'; Table 1 (conf) ...dumpblock (void)putc('\n', fx); for(i = 0;i < 2;i++){ if (*out[i] && (*out[i] != ' ' 11 *(ρo[i]) !='')){ if(i==0) nums(i); if(i==0&&*out[l]) stars(); putline(i); if(i==0&&*out[l]) fprintf(fx, star); if(i==l) nums(i); } /* * put out a number line: dumpblockO */ static nums(ix) nums int ix; /* index in outQ holding seq line */ { char nliπe[P_LINE]; register i, j; register char for (pn = nline, i = 0; i < lmax+P SPC; i+ + , pn+ +) *pn = ' '; for (i = nc[ix], py = out[ix]; *py; py+ +, pn+ +) { if(*py==" ||*py== '-') *pn= ' '; else { if (i%10 == 011 (i == 1 && ncfix] != 1)) { j = (i < 0)? -i : i; for (px = pn; j; j /= 10, px~) *px=j%10+ '0'; if(i<0) *px = '-'; } else *pn ; i++; } } *pn = '\0'; ncfix] = i; for (pn = nline; *pn; pn+ +) (void) putc(*pn, fx); (void)putc('\n', fx); } /* * put out a line (name, [num], seq, [num]): dumpblockO */ static putiine(ix) putline int ix; { Table 1 fcont') ...putline int i; register char *px; for (px = namexfix], i = 0; *px&& *px != ':'; px+ + , i++) (void) putc(*px, fx); for (; i < lmax+P_SPC; i++) (void)putc(' \fx); /* these count from 1: * niQ is current element (from 1) * ncQ is number at start of current line */ for (px = outfix]; *px; px++) (void) putc(*px&0x7F, fx); (void)putc('\n', fx); } /* * put a line of stars (seqs always in outfO], outfl]): dumpblockO */ static stars() stars int i; register char *p0, *pl, ex, *px; if (!*out[0] |,| (*out[0] == • '&& *(po[0]) == ' ') 11 !*out[l] 11 (*out[l] ==''&& *(po[l]) == '')) return; px = star; for (i = lmax+P SPC; i; i~) *px++ = ' '; for (pO = outfO], pi = outfl]; *p0 && *pl; p0++, pl + +) { if (isalpha(*p0) && isalpha(*pl)) { if (xbm[*p0-'A']&xbm[*pl-'A']) { ex = '*'; nm++; } elseif(!dna&&_day[*pO-'A'][*pl-'A'] > 0) ex = '.'; else } else ex = *px+ + = ex; *px++ = '\n'; *px = '\0'; Table 1 (conf) /* * strip path or prefix from pn, return len: pr_align() */ static stripname(pn) stripname char *pn; /* file name (may be path) */ { register char *px, *py; py = 0; for (px : = pn; *px; px+ +) if (*px = = = V) py = px + 1; if y) (void) strcpyφn, py); return(strlen(pn)) ; Table 1 (conf) /* * cleanupO - cleanup any tmp file * getseq() — read in seq, set dna, len, maxlen * g_calloc() -- calloc() with error checkin * readjmpsO — get the good jmps, from tmp file if necessary * writejmpsO -- write a filled array of jmps to a tmp file: nw() */ include "nw.h" #include <sys/file.h> char *jname = "/tmp/homgXXXXXX"; /* tmp file for jmps */ FILE *fj; int cleanupO; /* cleanup tmp file */ long lseek(); /* * remove any tmp file if we blow */ cleanup© cleanup int { if (® (void) unlink(jname); exit(i); /* * read, return ptr to seq, set dna, len, maxlen * skip lines starting with ' ; ' , ' < ' , or ' > ' * seq in upper or lower case */ char * getseq(file, len) getseq char *file; /* file name */ int *len; /* seq len */ { char line[1024], *pseq; register char *px, *py; int natgc, tlen; FILE *fp; if ((fp = fopen(file,"r")) == 0) { fprintf(stderr,"%s: can't read %s\n", prog, file); exit(l); } tlen = natgc = 0; while (fgets(line, 1024, fp)) { if (*line = = ';' | | *line = = ' < ' | | *line == ' > ') continue; for (px = line; *px != '\n'; px+ +) if (isupper(*px) 1 1 islower(*px)) tlen+ + ; } if ((pseq = malloc((unsigned)(tlen+6))) = = 0) { fprintf(stderr,"%s: malloc() failed to get %d bytes for %s\n", prog, tlen+6, file); exit(l); } pseqfO] = pseqfl] = pseq[2] = pseq[3] = '\0'; Table 1 (conf) ...getseq py = pseq + 4; *len = tlen; rewind(fp); while (fgets(line, 1024, fp)) { if (*line = = ';' | | *Iine = = ' < ' | | *line = = ' > ') continue; for (px = line; *px ! = '\n'; px+ +) { if (isupper(*px)) *py+ + = *px; else if (islower(*px)) *py+ + = toupper(*ρx); if (index("ATGCU",*(py-l))) natgc+ + ; } } *py++ = '\0'; *py = '\0'; (void) fclose(fp); dna = natgc > (tIen 3); return(pseq+4); } char * g_calloc(msg, nx, sz) g_CallθC char *msg; /* program, calling routine */ int nx, sz; /* number and size of elements */ { char *px, *calloc(); if ((px = calloc((unsigned)nx, (unsigned)sz)) = = 0) { if (*msg) { fpriπtf(stderr, "%s: g_calloc() failed %s (n= %d, sz= %d)\n", prog, msg, nx, sz); exit(l); } } returnφx); } /* * get final jmps from dxf] or tmp file, set ppfj, reset dmax: main() */ readjmpsQ readjmps { int fd = -1; int siz, iO, il; register i, j, xx; if (fj) { (void) fclose(fj); if ((fd = open(jname, OJRDONLY, 0)) < 0) { fprintf(stderr, "%s: can't open() %s\n", prog, jname); cleanup(l); } } for (i = iO = il = 0, dmaxO = dmax, xx = lenO; ; i++) { while (1) { for (j = dx[dmax].ijmp; j > = 0 && dx[dmax].jp.xfj] > = xx; j-) : Table 1 (conf) ...readjmps if (j < 0 && dxfdmax]. offset && fj) { (void) lseek(fd, dxfdmax]. offset, 0); (void) read(fd, (char *)&dx[dmax].jp, sizeof(struct jmp)); (void) read(fd, (char *)&dx[dmax]. offset, sizeof(dx[dmax]. offset)); dx[dmax].ijmp = MAXJMP- 1; } else break; } if (i > = JMPS) { fprintf(stderr, " %s: too many gaps in alignmentW, prog); cleanup(l); if (j > = 0) { siz = dxfdmax] jp.nfj]; xx = dxfdmax] .jp.xfj]; dmax + = siz; if (siz < 0) { /* gap in second seq */ pp[l].n[il] = -siz; xx + = siz; /* id = xx - yy + lenl - 1 */ pp[l].x[il] = xx - dmax + lenl - 1; gapy+ + ; ngapy -= siz; /* ignore MAXGAP when doing endgaps */ siz = (-siz < MAXGAP 1 1 endgaps)? -siz : MAXGAP; il + +; } else if (siz > 0) { /* gap in first seq */ pp[0].n[i0] = siz; pp[0].x[i0] = xx; gapx+ + ; ngapx += siz; /* ignore MAXGAP when doing endgaps */ siz = (siz < MAXGAP 1 1 endgaps)? siz : MAXGAP; i0+ + ; } else break; } /* reverse the order of jmps */ for (j = 0, i0-; j < i0; j + + , i0-) { i = pp[0].nfj]; pp[0].n[j] = pp[0].n[i0]; pp[0].n[i0] = i; i = pp[0].x[j]; pp[0].x[j] = pp[0].x[i0]; pp[0].x[i0] = i; } for (j = 0, il-; j < il; j + + , il-) { i = pp[l].n[j]; pp[l].n[j] = pp[l].n[il]; pp[l].n[il] = i; i = pp[i]- χ ffl; pp[i]. χ ffl = pp[i]. χ pi]; pp[i]. χ [ϋ] = i; if (fd > = 0) (void) close(fd); if (fj) { (void) unlink(jname); fj = 0; offset = 0; } } Table 1 (conf) /* * write a filled jmp struct offset of the prev one (if any): nw() */ writejmps(ix) Wlitejmps int ix; { char *mktemp(); if (!fj) { if (mktemp(jname) < 0) { fprintf(stderr, "%s: can't mktempO %s\n", prog, jname); cleanup(l); } if ((fj = fopen(jname, "w")) = = 0) { fprintf(stderr, "%s: can't write %s\n", prog, jname); exit(l); } (void) fwrite((char *)&dx[ix] .jp, sizeof(struct jmp), 1, fj); (void) fwrite((char *)&dx[ix]. offset, sizeof (dx[ix]. offset), 1, fj); Table 2 PRO XXXXXXXXXXXXXXX (Length = 15 amino acids) Comparison Protein XXXXXYYYYYYY (Length = 12 amino acids) % amino acid sequence identity = (the number of identically matching amino acid residues between the two polypeptide sequences as determined by ALIGN-2) divided by (the total number of amino acid residues of the PRO polypeptide) = 5 divided by 15 = 33.3% Table 3 PRO XXXXXXXXXX (Length = 10 amino acids) Comparison Protein XXXXXYYYYYYZZYZ (Length = 15 amino acids) % amino acid sequence identity = (the number of identically matching amino acid residues between the two polypeptide sequences as determined by ALIGN-2) divided by (the total number of amino acid residues of the PRO polypeptide) = 5 divided by 10 = 50% Table 4 PRO-DNA NNNNNNNNNNNNNN (Length = 14 nucleotides) Comparison DNA NNNNNNLLLLLLLLLL (Length = 16 nucleotides) % nucleic acid sequence identity = (the number of identically matching nucleotides between the two nucleic acid sequences as determined by ALIGN-2) divided by (the total number of nucleotides of the PRO-DNA nucleic acid sequence) = 6 divided by 14 = 42.9% Table 5 PRO-DNA NNNNNNNNNNNN (Length = 12 nucleotides) Comparison DNA NNNNLLLVV (Length = 9 nucleotides) % nucleic acid sequence identity = (the number of identically matching nucleotides between the two nucleic acid sequences as determined by ALIGN-2) divided by (the total number of nucleotides of the PRO-DNA nucleic acid sequence) = 4 divided by 12 = 33.3% II. Compositions and Methods of the Invention A. Full-Length Bolekine Polypeptides The present invention provides newly identified and isolated nucleotide sequences encoding polypeptides referred to in the present application as Bolekine polypeptides. In particular, cDNAs encoding various Bolekine polypeptides have been identified and isolated, as disclosed in further detail in the Examples below. However, for sake of simplicity, in the present specification the protein encoded by the full length native nucleic acid molecules disclosed herein as well as all further native homologues and variants included in the foregoing definition of Bolekine, will be referred to as Bolekine, regardless of their origin or mode of preparation. As disclosed in the Examples below, Bolekine cDNA clone has been deposited with the ATCC. The actual nucleotide sequences of those clones can readily be determined by the skilled artisan by sequencing of the deposited clone using routine methods in the art. The predicted amino acid sequence can be determined from the nucleotide sequence using routine skill. For the Bolekine polypeptides and encoding nucleic acids described herein, Applicants have identified what is believed to be the reading frame best identifiable with the sequence information available at the time. B. Bolekine Polypeptide Variants In addition to the full-length native sequence Bolekine polypeptides described herein, it is contemplated that Bolekine variants can be prepared. Bolekine variants can be prepared by introducing appropriate nucleotide changes into the Bolekine DNA, and/or by synthesis of the desired Bolekine polypeptide. Those skilled in the art will appreciate that amino acid changes may alter post-translational processes of the Bolekine, such as changing the number or position of glycosylation sites or altering the membrane anchoring characteristics. Variations in the native full-length sequence Bolekine or in various domains of the Bolekine described herein, can be made, for example, using any of the techniques and guidelines for conservative and non- conservative mutations set forth, for instance, in U.S. Patent No. 5,364,934. Variations may be a substitution, deletion or insertion of one or more codons encoding the Bolekine that results in a change in the amino acid sequence of the Bolekine as compared with the native sequence Bolekine. Optionally the variation is by substitution of at least one amino acid with any other amino acid in one or more of the domains of the Bolekine. Guidance in deteπnining which amino acid residue may be inserted, substituted or deleted without adversely affecting the desired activity may be found by comparing the sequence of the Bolekine with that of homologous known protein molecules and minimizing the number of amino acid sequence changes made in regions of high homology. Amino acid substitutions can be the result of replacing one amino acid with another amino acid having similar structural and/or chemical properties, such as the replacement of a leucine with a serine, i.e., conservative amino acid replacements. Insertions or deletions may optionally be in the range of about 1 to 5 amino acids. The variation allowed may be determined by systematically making insertions, deletions or substitutions of amino acids in the sequence and testing the resulting variants for activity exhibited by the full- length or mature native sequence. Bolekine polypeptide fragments are provided herein. Such fragments may be truncated at the N- terminus or C-teπriinus, or may lack internal residues, for example, when compared with a full length native protein. Certain fragments lack amino acid residues that are not essential for a desired biological activity of the Bolekine polypeptide. Bolekine fragments may be prepared by any of a number of conventional techniques. Desired peptide fragments may be chemically synthesized. An alternative approach involves generating Bolekine fragments by enzymatic digestion, e.g., by treating the protein with an enzyme known to cleave proteins at sites defined by particular amino acid residues, or by digesting the DNA with suitable restriction enzymes and isolating the desired fragment. Yet another suitable technique involves isolating and amplifying a DNA fragment encoding a desired polypeptide fragment, by polymerase chain reaction (PCR). Oligonucleotides that define the desired termini of the DNA fragment are employed at the 5' and 3' primers in the PCR. Preferably, Bolekine polypeptide fragments share at least one biological and/or immunological activity with the native Bolekine polypeptide disclosed herein. In particular embodiments, conservative substitutions of interest are shown in Table 6 under the heading of preferred substitutions. If such substitutions result in a change in biological activity, then more substantial changes, denominated exemplary substitutions in Table 6, or as further described below in reference to amino acid classes, are introduced and the products screened. Table 6 Original Exemplary Preferred Residue Substitutions Substitutions Ala (A) val; leu; ile val Arg (R) lys; gin; asn lys Asn (N) gin; his; lys; arg gin Asp (D) glu glu Cys (C) ser ser Gln (Q) asn asn Glu (E) asp asp Gly (G) pro; ala ala His (H) asn; gin; lys; arg arg lie (I) leu; val; met; ala; phe; norleucine leu Leu (L) norleucine; ile; val; met; ala; phe ile Lys (K) arg; gin; asn arg Met (M) leu; phe; ile leu Phe (F) leu; val; ile; ala; tyr leu Pro (P) ala ala Ser (S) thr thr Thr (T) ser ser Trp (W) tyr; phe tyr Tyr (Y) trp; phe; thr; ser phe Val (V) ile; leu; met; phe; ala; norleucine leu Substantial modifications in function or immunological identity of the Bolekine polypeptide are accomplished by selecting substitutions that differ significantly in their effect on maintaining (a) the structure of the polypeptide backbone in the area of the substitution, for example, as a sheet or helical conformation, (b) the charge or hydrophobicity of the molecule at the target site, or (c) the bulk of the side chain. Naturally occurring residues are divided into groups based on common side-chain properties: (1) hydrophobic: norleucine, met, ala, val, leu, ile; (2) neutral hydrophilic: cys, ser, thr; (3) acidic: asp, glu; (4) basic: asn, gin, his, lys, arg; (5) residues that influence chain orientation: gly, pro; and (6) aromatic: trp, tyr, phe. Non-conservative substitutions will entail exchanging a member of one of these classes for another class . Such substituted residues also may be introduced into the conservative substitution sites or, more preferably, into the remaining (non-conserved) sites. The variations can be made using methods known in the art such as oligonucleotide-mediated (site- directed) mutagenesis, alanine scanning, and PCR mutagenesis. Site-directed mutagenesis [Carter et al., Nucl. Acids Res.. 13:4331 (1986); Zoller et al., Nucl. Acids Res.. 10:6487 (1987)], cassette mutagenesis [Wells et al., Gene, 34:315 (1985)], restriction selection mutagenesis [Wells et al., Philos. Trans. R. Soc. London SerA. 317:415 (1986)] or other known techniques can be performed on the cloned DNA to produce the Bolekine variant DNA. Scanning amino acid analysis can also be employed to identify one or more amino acids along a contiguous sequence. Among the preferred scanning amino acids are relatively small, neutral amino acids. Such amino acids include alanine, glycine, serine, and cysteine. Alanine is typically a preferred scanning amino acid among this group because it eliminates the side-chain beyond the beta-carbon and is less likely to alter the main- chain conformation of the variant [Cunningham and Wells, Science. 244: 1081-1085 (1989)]. Alanine is also typically preferred because it is the most common amino acid. Further, it is frequently found in both buried and exposed positions [Creighton, The Proteins, (W.H. Freeman & Co., N.Y.); Chothia, J. Mol. Biol.. 150:1 (1976)] . If alanine substitution does not yield adequate amounts of variant, an isoteric amino acid can be used. C. Modifications of Bolekine Covalent modifications of Bolekine are included within the scope of this invention. One type of covalent modification includes reacting targeted amino acid residues of a Bolekine polypeptide with an organic derivatizing agent that is capable of reacting with selected side chains or the N- or C- terminal residues of the Bolekine. Derivatization with bifunctional agents is useful, for instance, for crosslinking Bolekine to a water- insoluble support matrix or surface for use in the method for purifying anti-Bolekine antibodies, and vice-versa. Commonly used crosslinking agents include, e.g., l,l-bis(diazoacetyl)-2-phenylethane, glutaraldehyde, N- hydroxysuccinimide esters, for example, esters with 4-azidosalicylic acid, homobifunctional imidoesters, including chsuccinimidyl esters such as 3 ,3 '-dithiobis(succinimidylpropionate), bifunctional maleimides such as bis-N-maleimido-l,8-octane and agents such as methyl-3-[(p-azidophenyl)dithio]proρioimidate. Other modifications include deamidation of glutaminyl and asparaginyl residues to the corresponding glutamyl and aspartyl residues, respectively, hydroxylation of proline and lysine, phosphorylation of hydroxyl groups of seryl or threonyl residues, methylation of the α-amino groups of lysine, arginine, and histidine side chains [T.E. Creighton, Proteins: Structure and Molecular Properties. W.H. Freeman & Co., San Francisco, pp. 79-86 (1983)], acetylation of the N-terminal amine, and amidation of any C-terminal carboxyl group. Another type of covalent modification of the Bolekine polypeptide included within the scope of this invention comprises altering the native glycosylation pattern of the polypeptide. "Altering the native glycosylation pattern" is intended for purposes herein to mean deleting one or more carbohydrate moieties found in native sequence Bolekine (either by removing the underlying glycosylation site or by deleting the glycosylation by chemical and/or enzymatic means), and/or adding one or more glycosylation sites that are not present in the native sequence Bolekine. In addition, the phrase includes qualitative changes in the glycosylation of the native proteins, involving a change in the nature and proportions of the various carbohydrate moieties present. Addition of glycosylation sites to the Bolekine polypeptide may be accomplished by altering the amino acid sequence. The alteration may be made, for example, by the addition of, or substitution by, one or more serine or threonine residues to the native sequence Bolekine (for O-linked glycosylation sites). The Bolekine amino acid sequence may optionally be altered through changes at the DNA level, particularly by mutating the DNA encoding the Bolekine polypeptide at preselected bases such that codons are generated that will translate into the desired amino acids. Another means of increasing the number of carbohydrate moieties on the Bolekine polypeptide is by chemical or enzymatic coupling of glycosides to the polypeptide. Such methods are described in the art, e.g. , in WO 87/05330 published 11 September 1987, and in Aplin and Wriston, CRC Crit. Rev. Biochem., pp. 259- 306 (1981). Removal of carbohydrate moieties present on the Bolekine polypeptide may be accomplished chemically or enzymatically or by mutational substitution of codons encoding for amino acid residues that serve as targets for glycosylation. Chemical deglycosylation techniques are known in the art and described, for instance, by Hakimuddin, et al., Arch. Biochem. Biophys.. 259:52 (1987) and by Edge et al., Anal. Biochem.. 118:131 (1981). Enzymatic cleavage of carbohydrate moieties on polypeptides can be achieved by the use of a variety of endo- and exo-glycosidases as described by Thotakura et al., Meth. Enzymol.. 138:350 (1987). Another type of covalent modification of Bolekine comprises linking the Bolekine polypeptide to one of a variety of nonproteinaceous polymers, e.g., polyethylene glycol (PEG), polypropylene glycol, or polyoxyalkylenes, in the manner set forth in U.S. Patent Nos. 4,640,835; 4,496,689; 4,301,144; 4,670,417; 4,791,192 or 4,179,337. The Bolekine of the present invention may also be modified in a way to form a ehimeric molecule comprising Bolekine fused to another, heterologous polypeptide or amino acid sequence. In one embodiment, such a ehimeric molecule comprises a fusion of the Bolekine with a tag polypeptide which provides an epitope to which an anti-tag antibody can selectively bind. The epitope tag is generally placed at the amino- or carboxyl- terminus of the Bolekine. The presence of such epitope-tagged forms of the Bolekine can be detected using an antibody against the tag polypeptide. Also, provision of the epitope tag enables the Bolekine to be readily purified by affinity purification using an anti-tag antibody or another type of affinity matrix that binds to the epitope tag. Various tag polypeptides and their respective antibodies are well known in the art. Examples include poly-histidine (poly-his) or poly-histidine-glycine (poly-his-gly) tags; the flu HA tag polypeptide and its antibody 12CA5 [Field et al. , Mol. Cell. Biol.. 8:2159-2165 (1988)]; the c-myc tag and the 8F9, 3C7, 6E10, G4, B7 and9E10 antibodies thereto [Evan etal., Molecular and Cellular Biology, 5:3610-3616 (1985)]; and the Herpes Simplex virus glycoprotein D (gD) tag and its antibody [Paborsky et al., Protein Engineering. 3(6):547-553 (1990)]. Other tag polypeptides include the Flag-peptide [Hopp et al., BioTechnology, 6:1204-1210 (1988)]; the KT3 epitope peptide [Martin et al., Science. 255:192-194 (1992)]; an α-tubulin epitope peptide [Skinner et al., J. Biol. Chem., 266:15163-15166 (1991)]; and the T7 gene 10 protein peptide tag [Lutz-Freyermuth et al., Proc. Natl. Acad. Sci. USA. 87:6393-6397 (1990)]. In an alternative embodiment, the ehimeric molecule may comprise a fusion of the Bolekine with an immunoglobulin or a particular region of an immunoglobulin. For a bivalent form of the ehimeric molecule (also referred to as an "immunoadhesin"), such a fusion could be to the Fc region of an IgG molecule. The Ig fusions preferably include the substitution of a soluble (transmembrane domain deleted or inactivated) form of a Bolekine polypeptide in place of at least one variable region within an Ig molecule. In a particularly preferred embodiment, the immunoglobulin fusion includes the hinge, CH2 and CH3, or the hinge, CHI, CH2 and CH3 regions of an IgGl molecule. For the production of immunoglobulin fusions see also US Patent No. 5,428, 130 issued June 27, 1995. D. Preparation of Bolekine The description below relates primarily to production of Bolekine by culturing cells transformed or transfected with a vector containing Bolekine nucleic acid. It is, of course, contemplated that alternative methods, which are well known in the art, may be employed to prepare Bolekine. For instance, the Bolekine sequence, or portions thereof, may be produced by direct peptide synthesis using solid-phase techniques [see, e.g. , Stewart et al. , Solid-Phase Peptide Synthesis, W.H. Freeman Co. , San Francisco, CA (1969); Merrifield, J. Am. Chem. Soc, 85:2149-2154 (1963)]. In vitro protein synthesis may be performed using manual techniques or by automation. Automated synthesis may be accomplished, for instance, using an Applied Biosystems Peptide Synthesizer (Foster City, CA) using manufacturer's instructions. Various portions of the Bolekine may be chemically synthesized separately and combined using chemical or enzymatic methods to produce the full-length Bolekine. 1. Isolation of DNA Encoding Bolekine DNA encoding Bolekine may be obtained from a cDNA library prepared from tissue believed to possess the Bolekine mRNA and to express it at a detectable level. Accordingly, human Bolekine DNA can be conveniently obtained from a cDNA library prepared from human tissue, such as described in the Examples. The Bolekine-encoding gene may also be obtained from a genomic library or by known synthetic procedures (e.g., automated nucleic acid synthesis). Libraries can be screened with probes (such as antibodies to the Bolekine or oligonucleotides of at least about 20-80 bases) designed to identify the gene of interest or the protein encoded by it. Screening the cDNA or genomic library with the selected probe may be conducted using standard procedures, such as described in Sambrook et al. , Molecular Cloning: A Laboratory Manual (New York: Cold Spring Harbor Laboratory Press, 1989). An alternative means to isolate the gene encoding Bolekine is to use PCR methodology [Sambrook et al., supra; Dieffenbach et al., PCR Primer: A Laboratory Manual (Cold Spring Harbor Laboratory Press, 1995)]. The Examples below describe techniques for screening a cDNA library. The oligonucleotide sequences selected as probes should be of sufficient length and sufficiently unambiguous that false positives are rninimized. The oligonucleotide is preferably labeled such that it can be detected upon hybridization to DNA in the library being screened. Methods of labeling are well known in the art, and include the use of radiolabels like 32 P-labeled ATP, biotinylation or enzyme labeling. Hybridization conditions, including moderate stringency and high stringency, are provided in Sambrook et al., supra. Sequences identified in such library screening methods can be compared and aligned to other known sequences deposited and available in public databases such as GenBank or other private sequence databases. Sequence identity (at either the amino acid or nucleotide level) within defined regions of the molecule or across the full-length sequence can be determined using methods known in the art and as described herein. Nucleic acid having protein coding sequence may be obtained by screening selected cDNA or genomic libraries using the deduced amino acid sequence disclosed herein for the first time, and, if necessary, using conventional primer extension procedures as described in Sambrook et al., supra, to detect precursors and processing intermediates of mRNA that may not have been reverse-transcribed into cDNA. 2. Selection and Transformation of Host Cells Host cells are transfected or transformed with expression or cloning vectors described herein for Bolekine production and cultured in conventional nutrient media modified as appropriate for inducing promoters, selecting transformants, or amplifying the genes encoding the desired sequences. The culture conditions, such as media, temperature, pH and the like, can be selected by the skilled artisan without undue experimentation. In general, principles, protocols, and practical techniques for maximizing the productivity of cell cultures can be found in Mammalian Cell Biotechnology: a Practical Approach. M. Butler, ed. (IRL Press, 1991) and Sambrook et al., supra. Methods of eukaryotic cell transfection and prokaryotic cell transformation are known to the ordinarily skilled artisan, for example, CaCl 2 , CaP0 4 , liposome-mediated and electroporation. Depending on the host cell used, transformation is performed using standard techniques appropriate to such cells. The calcium treatment employing calcium chloride, as described in Sambrook et al. , supra, or electroporation is generally used for prokaryotes. Infection with Agrobacterium tumefaciens is used for transformation of certain plant cells, as described by Shaw et al. , Gene, 23 :315 (1983) and WO 89/05859 published 29 June 1989. For mammalian cells without such cell walls, the calcium phosphate precipitation method of Graham and van der Eb, Virology, 52:456-457 (1978) can be employed. General aspects of mammalian cell host system transfections have been described in U.S. Patent No. 4,399,216. Transformations into yeast are typically carried out according to the method of Van Solingen et al. , J. Bact..130:946 (1977) and Hsiao et al. , Proc. Natl. Acad. Sci. (USA). 76:3829 (1979). However, other methods for introducing DNA into cells, such as by nuclear microinjection, electroporation, bacterial protoplast fusion with intact cells, or polycations, e.g., polybrene, polyornithine, may also be used. For various techniques for transforming mammalian cells, see Keown et al., Methods in Enzvmology. 185:527-537 (1990) and Mansour et al., Nature. 336:348-352 (1988). Suitable host cells for cloning or expressing the DNA in the vectors herein include prokaryote, yeast, or higher eukaryote cells. Suitable prokaryotes include but are not limited to eubacteria, such as Gram-negative or Gram-positive organisms, for example, Enterobacteriaceae such as E. coli. Various E. coli strains are publicly available, such as E. coli K12 strain MM294 (ATCC 31,446); E. coli X1776 (ATCC 31,537); E. coli strain W3110 (ATCC 27,325) and K5 772 (ATCC 53,635). Other suitable prokaryotic host cells include Enterobacteriaceae such as Escherichia, e.g. , E. coli, Enterobacter, Erwinia, Klebsiella, Proteus, Salmonella, e.g., Salmonella typhimurium, Serratia, e.g., Serratia marcescans, and Shigella, as well as Bacilli such as B. subtilis and B. licheniformis (e.g., B. licheniformis 41P disclosed in DD 266,710 published 12 April 1989), Pseudomonas such as P. aeruginosa, and Streptomyces. These examples are illustrative rather than limiting. Strain W3110 is one particularly preferred host or parent host because it is a common host strain for recombinant DNA product fermentations. Preferably, the host cell secretes minimal amounts of proteolytic enzymes. For example, strain W3110 may be modified to effect a genetic mutation in the genes encoding proteins endogenous to the host, with examples of such hosts including E. coli W3110 strain 1 A2, which has the complete genotype tonA ; E. coli W3110 strain 9E4, which has the complete genotype tonA ptr3; E. coli W3110 strain 27C7 (ATCC 55,244), which has the complete genotype tonA ptr 3 phoA El 5 (argF-lac)169 degP ompTkaif; E. coli W3110 strain 37D6, which has the complete genotype tonA ptr3 phoA E15 (argF-lac)169 degP ompT rbs7 ilvG kan r ; E. coli W3110 strain 40B4, which is strain 37D6 with a non-kanamycin resistant degP deletion mutation; andani?. coli strain having mutant periplasmic protease disclosed in U.S. PatentNo. 4,946,783 issued 7 August 1990. Alternatively, in vitro methods of cloning, e.g., PCR or other nucleic acid polymerase reactions, are suitable. In addition to prokaryotes, eukaryotic microbes such as filamentous fungi or yeast are suitable cloning or expression hosts for Bolekine-encoding vectors. Saccharomyces cerevisiae is a commonly used lower eukaryotic host microorganism. Others include Schizosaccharotnyces pombe (Beach and Nurse, Nature. 290: 140 [1981]; EP 139,383 published 2 May 1985); Kluyveromyces hosts (U.S. Patent No. 4,943,529; Fleer et al., Bio/Technology. 9:968-975 (1991)) such as, e.g., K. lactis (MW98-8C, CBS683, CBS4574; Louvencourtetal., J. Bacteriol.. 154(2):737-742 [1983]), K.fragilis (ATCC 12,424), K. bulgaricus (ATCC 16,045), K. wickeramii (ATCC 24,178), K. waltii (ATCC 56,500), K. drosophilarum (ATCC 36,906; Van den Berg et al., Bio/Technology. 8:135 (1990)), K. thermotolerans, and . marxianus; yarrowia (EP 402,226); Pichia pastoris (EP 183,070; Sreekrishna et al., J. Basic Microbiol.. 28:265-278 [1988]); Candida; Trichoderma reesia (EP 244,234); Neurospora crassa (Case et al. , Proc. Natl. Acad. Sci. USA.76:5259-5263 [1979]); Sclτwanniomyces such as Schwanniomyces occidentalis (EP 394,538 published 31 October 1990); and filamentous fungi such as, e.g. , Neurospora, Penicillium, Tolypocladium (WO 91/00357 published 10 January 1991), mάAspergillus hosts such as A. nidulans (Ballance et al., Biochem. Biophys. Res. Commun.. 112:284-289 [1983]; Tilburn et al., Gene. 26:205-221 [1983]; Yeltonetal.. Proc. Natl. Acad. Sci. USA. 81: 1470-1474 [1984]) and A niger (Kelly and Hynes, EMBO J.. 4:475-479 [1985]). Methylotropic yeasts are suitable herein and include, but are not limited to, yeast capable of growth on methanol selected from the genera consisting of Hansenula, Candida, Kloeckera, Pichia, Saccharomyces, Torulopsis, saάPiodotorula. A list of specific species that are exemplary of this class of yeasts may be found in C. Anthony, The Biochemistry of Methylotrophs. 269 (1982). Suitable host cells for the expression of glycosylated Bolekine are derived from multicellular organisms . Examples of invertebrate cells include insect cells such as Drosophila S2 and Spodoptera Sf9, as well as plant cells. Examples of useful mammalian host cell lines include Chinese hamster ovary (CHO) and COS cells. More specific examples include monkey kidney CV1 line transformed by SV40 (COS-7, ATCC CRL 1651); human embryonic kidney line (293 or 293 cells subcloned for growth in suspension culture, Graham et al. , Gen Virol.. 36:59 (1977)); Chinese hamster ovary cells/-DHFR (CHO, Urlaub and Chasin, Proc. Natl. Acad. Sci. USA. 77:4216 (1980)); mouse sertoli cells (TM4, Mather, Biol. Reprod..23:243-251 (1980)); human lung cells (W138, ATCC CCL 75); human liver cells (Hep G2, HB 8065); and mouse mammary tumor (MMT 060562, ATCC CCL51). The selection of the appropriate host cell is deemed to be within the skill in the art. 3. Selection and Use of a Replicable Vector The nucleic acid (e.g., cDNA or genomic DNA) encoding Bolekine may be inserted into a replicable vector for cloning (amplification of the DNA) or for expression. Various vectors are publicly available. The vector may, for example, be in the form of a plasmid, cosmid, viral particle, or phage. The appropriate nucleic acid sequence may be inserted into the vector by a variety of procedures. In general, DNA is inserted into an appropriate restriction endonuclease site(s) using techniques known in the art. Vector components generally include, but are not limited to, one or more of a signal sequence, an origin of replication, one or more marker genes, an enhancer element, a promoter, and a transcription termination sequence. Construction of suitable vectors containing one or more of these components employs standard ligation techniques which are known to the skilled artisan. The Bolekine may be produced recombinantly not only directly, but also as a fusion polypeptide with a heterologous polypeptide, which may be a signal sequence or other polypeptide having a specific cleavage site at the N-terminus of the mature protein or polypeptide. In general, the signal sequence may be a component of the vector, or it may be a part of the Bolekine-encoding DNA that is inserted into the vector. The signal sequence may be a prokaryotic signal sequence selected, for example, from the group of the alkaline phosphatase, penicillinase, Ipp, or heat-stable enterotoxin JJ leaders. For yeast secretion the signal sequence may be, e.g., the yeast invertase leader, alpha factor leader (including Saccharomyces and Kluyveromyces α-factor leaders, the latter described in U.S. Patent No. 5,010,182), or acid phosphatase leader, the C. albicans glucoamylase leader (EP 362,179 published 4 April 1990), or the signal described in WO 90/13646 published 15 November 1990. In mammalian cell expression, mammalian signal sequences may be used to direct secretion of the protein, such as signal sequences from secreted polypeptides of the same or related species, as well as viral secretory leaders. Both expression and cloning vectors contain a nucleic acid sequence that enables the vector to replicate in one or more selected host cells. Such sequences are well known for a variety of bacteria, yeast, and viruses. The origin of replication from the plasmid pBR322 is suitable for most Gram-negative bacteria, the 2μ plasmid origin is suitable for yeast, and various viral origins (SV40, polyoma, adenovirus, VSV or BPV) are useful for cloning vectors in mammalian cells. Expression and cloning vectors will typically contain a selection gene, also termed a selectable marker. Typical selection genes encode proteins that (a) confer resistance to antibiotics or other toxins, e.g., ampicillin, neomycin, methotrexate, or tetracycline, (b) complement auxotrophic deficiencies, or (c) supply critical nutrients not available from complex media, e.g., the gene encoding D-alanine racemase for Bacilli. An example of suitable selectable markers for mammalian cells are those that enable the identification of cells competent to take up the Bolekine-encoding nucleic acid, such as DHFR or thymidine kinase. An appropriate host cell when wild-type DHFR is employed is the CHO cell line deficient in DHFR activity, prepared and propagated as described by Urlaub et al., Proc. Natl. Acad. Sci. USA. 77:4216 (1980). A suitable selection gene for use in yeast is the trpl gene present in the yeast plasmid YRp7 [Stinchcomb et al., Nature. 282:39 (1979); Kingsman et al., Gene. 7:141 (1979); Tschemper et al., Gene, 10:157 (1980)]. The trpl gene provides a selection marker for a mutant strain of yeast lacking the ability to grow in tryptophan, for example, ATCC No. 44076 or PEP4-1 [Jones, Genetics. 85:12 (1977)]. Expression and cloning vectors usually contain a promoter operably linked to the Bolekine-encoding nucleic acid sequence to direct mRNA synthesis. Promoters recognized by a variety of potential host cells are well known. Promoters suitable for use with prokaryotic hosts include the β-lactamase and lactose promoter systems [Chang et al., Nature. 275:615 (1978); Goeddel et al., Nature, 281:544 (1979)], alkaline phosphatase, a tryptophan (trp) promoter system [Goeddel, Nucleic Acids Res.. 8:4057 (1980); EP 36,776], and hybrid promoters such as the tae promoter [deBoer et al., Proc. Natl. Acad. Sci. USA. 80:21-25 (1983)]. Promoters for use in bacterial systems also will contain a Shine-Dalgarno (S.D.) sequence operably linked to the DNA encoding Bolekine. Examples of suitable promoting sequences for use with yeast hosts include the promoters for 3- phosphoglycerate kinase [Hitzeman et al., J. Biol. Chem.. 255:2073 (1980)] or other glycolytic enzymes [Hess et al., J. Adv. Enzyme Reg., 7:149 (1968); Holland, Biochemistry, 17:4900 (1978)], such as enolase, glyceraldehyde-3-phosphatedehydrogenase, hexokinase, pyruvate decarboxylase, phosphofructokinase, glucose- 6-phosphate isomerase, 3-phosphoglycerate mutase, pyruvate kinase, triosephosphate isomerase, phosphoglucose isomerase, and glucokinase. Other yeast promoters, which are inducible promoters having the additional advantage of transcription controlled by growth conditions, are the promoter regions for alcohol dehydrogenase 2, isocytochrome C, acid phosphatase, degradative enzymes associated with nitrogen metabolism, metallothionein, glyceraldehyde-3- phosphate dehydrogenase, and enzymes responsible for maltose and galactose utilization. Suitable vectors and promoters for use in yeast expression are further described in EP 73,657. Bolekine transcription from vectors in mammalian host cells is controlled, for example, by promoters obtained from the genomes of viruses such as polyoma virus, fowlpox virus (UK 2,211,504 published 5 July 1989), adenovirus (such as Adenovirus 2), bovine papilloma virus, avian sarcoma virus, cytomegalovirus, a retrovirus, hepatitis-B virus and Simian Virus 40 (SV40), from heterologous mammalian promoters, e.g., the actin promoter or an immunoglobulin promoter, and from heat-shock promoters, provided such promoters are compatible with the host cell systems. Transcription of a DNA encoding the Bolekine by higher eukaryotes may be increased by inserting an enhancer sequence into the vector. Enhancers are cis-acting elements of DNA, usually about from 10 to 300 bp, that act on a promoter to increase its transcription. Many enhancer sequences are now known from mammalian genes (globin, elastase, albumin, α-fetoprotein, and insulin). Typically, however, one will use an enhancer from a eukaryotic cell virus. Examples include the SV40 enhancer on the late side of the replication origin (bp 100-270), the cytomegalovirus early promoter enhancer, the polyoma enhancer on the late side of the replication origin, and adenovirus enhancers. The enhancer may be spliced into the vector at a position 5' or 3' to the Bolekine coding sequence, but is preferably located at a site 5' from the promoter. Expression vectors used in eukaryotic host cells (yeast, fungi, insect, plant, animal, human, or nucleated cells from other multicellular organisms) will also contain sequences necessary for the termination of transcription and for stabilizing the mRNA. Such sequences are commonly available from the 5' and, occasionally 3 ' , untranslated regions of eukaryotic or viral DNAs or cDNAs . These regions contain nucleotide segments transcribed as polyadenylated fragments in the untranslated portion of the mRNA encoding Bolekine. Still other methods, vectors, and host cells suitable for adaptation to the synthesis of Bolekine in recombinant vertebrate cell culture are described in Gething et al., Nature, 293:620-625 (1981); Mantei et al., Nature. 281:40-46 (1979); EP 117,060; and EP 117,058. 4. Detecting Gene Amplification/Expression Gene amplification and/or expression may be measured in a sample directly, for example, by conventional Southern blotting, Northern blotting to quantitate the transcription of mRNA [Thomas, Proc. Natl. Acad. Sci. USA. 77:5201-5205 (1980)], dot blotting (DNA analysis), or in situ hybridization, using an appropriately labeled probe, based on the sequences provided herein. Alternatively, antibodies may be employed that can recognize specific duplexes, including DNA duplexes, RNA duplexes, and DNA-RNA hybrid duplexes or DNA-protein duplexes. The antibodies in turn may be labeled and the assay may be carried out where the duplex is bound to a surface, so that upon the formation of duplex on the surface, the presence of antibody bound to the duplex can be detected. Gene expression, alternatively, may be measured by immunological methods, such as immunohistochemical staining of cells or tissue sections and assay of cell culture or body fluids, to quantitate directly the expression of gene product. Antibodies useful for immunohistochemical staining and/or assay of sample fluids may be either monoclonal or polyclonal, and may be prepared in any mammal. Conveniently, the antibodies may be prepared against a native sequence Bolekine polypeptide or against a synthetic peptide based on the DNA sequences provided herein or against exogenous sequence fused to Bolekine DNA and encoding a specific antibody epitope. 5. Purification of Polypeptide Forms of Bolekine may be recovered from culture medium or from host cell lysates. If membrane- bound, it can be released from the membrane using a suitable detergent solution (e.g. Triton-X 100) or by enzymatic cleavage . Cells employed in expression of Bolekine can be disrupted by various physical or chemical means, such as freeze-thaw cycling, sonication, mechanical disruption, or cell lysing agents. It may be desired to purify Bolekine from recombinant cell proteins or polypeptides. The following procedures are exemplary of suitable purification procedures: by fractionation on an ion-exchange column; ethanol precipitation; reverse phase HPLC; chromatography on silica or on a cation-exchange resin such as DEAE; chromatofocusing; SDS-PAGE; ammonium sulfate precipitation; gel filtration using, for example, Sephadex G-75; protein A Sepharose columns to remove contaminants such as IgG; and metal chelating columns to bind epitope-tagged forms of the Bolekine. Various methods of protein purification may be employed and such methods are known in the art and described for example in Deutscher, Methods in Enzymology, 182 (1990); Scopes, Protein Purification: Principles and Practice. Springer-Verlag, New York (1982). The purification step(s) selected will depend, for example, on the nature of the production process used and the particular Bolekine produced. E. Uses for Bolekine Nucleotide sequences (or their complement) encoding Bolekine have various applications in the art of molecular biology, including uses as hybridization probes, in chromosome and gene mapping and in the generation of anti-sense RNA and DNA. Bolekine nucleic acid will also be useful for the preparation of Bolekine polypeptides by the recombinant techniques described herein. The full-length native sequence Bolekine gene, or portions thereof, may be used as hybridization probes for a cDNA library to isolate the full-length Bolekine cDNA or to isolate still other cDNAs (for instance, those encoding naturally-occurring variants of Bolekine or Bolekine from other species) which have a desired sequence identity to the native Bolekine sequence disclosed herein. Optionally, the length of the probes will be about 20 to about 50 bases. The hybridization probes may be derived from at least partially novel regions of the full length native nucleotide sequence wherein those regions may be determined without undue experimentation or from genomic sequences including promoters, enhancer elements and introns of native sequence Bolekine. By way of example, a screening method will comprise isolating the coding region of the Bolekine gene using the known DNA sequence to synthesize a selected probe of about 40 bases. Hybridization probes may be labeled by a variety of labels, including radionucleotides such as 32 P or 35 S, or enzymatic labels such as alkaline phosphatase coupled to the probe via avidin/biotin coupling systems. Labeled probes having a sequence complementary to that of the Bolekine gene of the present invention can be used to screen libraries of human cDNA, genomic DNA or mRNA to determine which members of such libraries the probe hybridizes to. Hybridization techniques are described in further detail in the Examples below. Any EST sequences disclosed in the present application may similarly be employed as probes, using the methods disclosed herein. Other useful fragments of the Bolekine nucleic acids include antisense or sense oligonucleotides comprising a singe-stranded nucleic acid sequence (either RNA or DNA) capable of binding to target Bolekine mRNA (sense) or Bolekine DNA (antisense) sequences. Antisense or sense oligonucleotides, according to the present invention, comprise a fragment of the coding region of Bolekine DNA. Such a fragment generally comprises at least about 14 nucleotides, preferably from about 14 to 30 nucleotides. The ability to derive an antisense or a sense oligonucleotide, based upon a cDNA sequence encoding a given protein is described in, for example, Stein and Cohen (Cancer Res. 48:2659, 1988) and van der Krol et al. (BioTechniques 6:958, 1988). Binding of antisense or sense oligonucleotides to target nucleic acid sequences results in the formation of duplexes that block transcription or translation of the target sequence by one of several means, including enhanced degradation of the duplexes, premature termination of transcription or translation, or by other means. The antisense oligonucleotides thus may be used to block expression of Bolekine proteins. Antisense or sense oligonucleotides further comprise oligonucleotides having modified sugar-phosphodiester backbones (or other sugar linkages, such as those described in WO 91/06629) and wherein such sugar linkages are resistant to endogenous nucleases. Such oligonucleotides with resistant sugar linkages are stable in vivo (i.e., capable of resisting enzymatic degradation) but retain sequence specificity to be able to bind to target nucleotide sequences . Other examples of sense or antisense oligonucleotides include those oligonucleotides which are covalently linked to organic moieties, such as those described in WO 90/10048, and other moieties that increases affinity of the oligonucleotide for a target nucleic acid sequence, such as poly-(L-lysine). Further still, intercalating agents, such as ellipticine, and alkylating agents or metal complexes may be attached to sense or antisense oligonucleotides to modify binding specificities of the antisense or sense oligonucleotide for the target nucleotide sequence. Antisense or sense oligonucleotides may be introduced into a cell containing the target nucleic acid sequence by any gene transfer method, including, for example, CaP0 4 -mediated DNA transfection, electroporation, or by using gene transfer vectors such as Epstein-Barr virus. In a preferred procedure, an antisense or sense oligonucleotide is inserted into a suitable retroviral vector. A cell containing the target nucleic acid sequence is contacted with the recombinant retroviral vector, either in vivo or ex vivo. Suitable retroviral vectors include, but are not limited to, those derived from the murine retrovirus M-MuLV, N2 (a retrovirus derived from M-MuLV), or the double copy vectors designated DCT5A, DCT5B and DCT5C (see WO 90/13641). Sense or antisense oligonucleotides also may be introduced into a cell containing the target nucleotide sequence by formation of a conjugate with a ligand binding molecule, as described in WO 91/04753. Suitable ligand binding molecules include, but are not limited to, cell surface receptors, growth factors, other cytokines, or other ligands that bind to cell surface receptors. Preferably, conjugation of the ligand binding molecule does not substantially interfere with the ability of the ligand binding molecule to bind to its corresponding molecule or receptor, or block entry of the sense or antisense oligonucleotide or its conjugated version into the cell. Alternatively, a sense or an antisense oligonucleotide may be introduced into a cell containing the target nucleic acid sequence by formation of an oligonucleotide-lipid complex, as described in WO 90/10448. The sense or antisense oligonucleotide-lipid complex is preferably dissociated within the cell by an endogenous lipase . Antisense or sense RNA or DNA molecules are generally at least about 5 bases in length, about 10 bases in length, about 15 bases in length, about 20 bases in length, about 25 bases in length, about 30 bases in length, about 35 bases in length, about 40 bases in length, about 45 bases in length, about 50 bases in length, about 55 bases in length, about 60 bases in length, about 65 bases in length, about 70 bases in length, about 75 bases in length, about 80 bases in length, about 85 bases in length, about 90 bases in length, about 95 bases in length, about 100 bases in length, or more. The probes may also be employed in PCR techniques to generate a pool of sequences for identification of closely related Bolekine coding sequences. Nucleotide sequences encoding Bolekine can also be used to construct hybridization probes for mapping the gene which encodes that Bolekine and for the genetic analysis of individuals with genetic disorders. The nucleotide sequences provided herein may be mapped to a chromosome and specific regions of a chromosome using known techniques, such as in situ hybridization, linkage analysis against known chromosomal markers, and hybridization screening with libraries. When the coding sequences for Bolekine encode a protein which binds to another protein (example, where the Bolekine is a receptor), the Bolekine can be used in assays to identify the other proteins or molecules involved in the binding interaction. By such methods, inhibitors of the receptor/ligand binding interaction can be identified. Proteins involved in such binding interactions can also be used to screen for peptide or small molecule inhibitors or agonists of the binding interaction. Also, the receptor Bolekine can be used to isolate correlative ligand(s) . Screening assays can be designed to find lead compounds that mimic the biological activity of a native Bolekine or a receptor for Bolekine. Such screening assays will include assays amenable to high- throughput screening of chemical libraries, making them particularly suitable for identifying small molecule drug candidates. Small molecules contemplated include synthetic organic or inorganic compounds. The assays can be performed in a variety of formats, including protein-protein binding assays, biochemical screening assays, immunoassays and cell based assays, which are well characterized in the art. Nucleic acids which encode Bolekine or its modified forms can also be used to generate either transgenic animals or "knock out" animals which, in turn, are useful in the development and screening of therapeutically useful reagents. A transgenic animal (e.g. , a mouse or rat) is an animal having cells that contain a transgene, which transgene was introduced into the animal or an ancestor of the animal at a prenatal, e.g. , an embryonic stage. A transgene is a DNA which is integrated into the genome of a cell from which a transgenic animal develops. In one embodiment, cDNA encoding Bolekine can be used to clone genomic DNA encoding Bolekine in accordance with established techniques and the genomic sequences used to generate transgenic animals that contain cells which express DNA encoding Bolekine. Methods for generating transgenic animals, particularly animals such as mice or rats, have become conventional in the art and are described, for example, in U.S. Patent Nos. 4,736,866 and 4,870,009. Typically, particular cells would be targeted for Bolekine transgene incorporation with tissue-specific enhancers. Transgenic animals that include a copy of a transgene encoding Bolekine introduced into the germ line of the animal at an embryonic stage can be used to examine the effect of increased expression of DNA encoding Bolekine. Such animals can be used as tester animals for reagents thought to confer protection from, for example, pathological conditions associated with its overexpression. In accordance with this facet of the invention, an animal is treated with the reagent and a reduced incidence of the pathological condition, compared to untreated animals bearing the transgene, would indicate a potential therapeutic intervention for the pathological condition. Alternatively, non-human homologues of Bolekine can be used to construct a Bolekine "knock out" animal which has a defective or altered gene encoding Bolekine as a result of homologous recombination between the endogenous gene encoding Bolekine and altered genomic DNA encoding Bolekine introduced into an embryonic stem cell of the animal. For example, cDNA encoding Bolekine can be used to clone genomic DNA encoding Bolekine in accordance with established techniques . A portion of the genomic DNA encoding Bolekine can be deleted or replaced with another gene, such as a gene encoding a selectable marker which can be used to monitor integration. Typically, several kilobases of unaltered flanking DNA (both at the 5' and 3' ends) are included in the vector [see e.g., Thomas and Capecchi, Cell, 51:503 (1987) for a description of homologous recombination vectors] . The vector is introduced into an embryonic stem cell line (e.g. , by electroporation) and cells in which the introduced DNA has homologously recombined with the endogenous DNA are selected [see e.g., Li et al., Cell, 69:915 (1992)]. The selected cells are then injected into a blastocyst of an animal (e.g., a mouse or rat) to form aggregation chimeras [see e.g., Bradley, in Teratocarcinomas and Embryonic Stem Cells: A Practical Approach, E. J. Robertson, ed. (IRL, Oxford, 1987), pp. 113-152]. A ehimeric embryo can then be implanted into a suitable pseudopregnant female foster animal and the embryo brought to term to create a "knock out" animal. Progeny harboring the homologously recombined DNA in their germ cells can be identified by standard techniques and used to breed animals in which all cells of the animal contain the homologously recombined DNA. Knockout animals can be characterized for instance, for their ability to defend against certain pathological conditions and for their development of pathological conditions due to absence of the Bolekine polypeptide. Nucleic acid encoding the Bolekine polypeptides may also be used in gene therapy. In gene therapy applications, genes are introduced into cells in order to achieve in vivo synthesis of a therapeutically effective genetic product, for example for replacement of a defective gene. "Gene therapy" includes both conventional gene therapy where a lasting effect is achieved by a single treatment, and the administration of gene therapeutic agents, which involves the one time or repeated administration of a therapeutically effective DNA or mRNA. Antisense RNAs and DNAs can be used as therapeutic agents for blocking the expression of certain genes in vivo. It has already been shown that short antisense oligonucleotides can be imported into cells where they act as inhibitors, despite their low intracellular concentrations caused by their restricted uptake by the cell membrane. (Zamecnik et al. , Proc. Natl. Acad. Sci. USA 83:4143-4146 [1986]). The oligonucleotides can be modified to enhance their uptake, e.g. by substituting their negatively charged phosphodiester groups by uncharged groups. There are a variety of techniques available for introducing nucleic acids into viable cells. The techniques vary depending upon whether the nucleic acid is transferred into cultured cells in vitro, or in vivo in the cells of the intended host. Techniques suitable for the transfer of nucleic acid into mammalian cells in vitro include the use of liposomes, electroporation, microinjection, cell fusion, DEAE-dextran, the calcium phosphate precipitation method, etc. The currently preferred in vivo gene transfer techniques include transfection with viral (typically retroviral) vectors and viral coat protein-liposome mediated transfection (Dzau et al., Trends in Biotechnology 11, 205-210 [1993]). In some situations it is desirable to provide the nucleic acid source with an agent that targets the target cells, such as an antibody specific for a cell surface membrane protein or the target cell, a ligand for a receptor on the target cell, etc. Where liposomes are employed, proteins which bind to a cell surface membrane protein associated with endocytosis may be used for targeting and/or to facilitate uptake, e.g. capsid proteins or fragments thereof tropic for a particular cell type, antibodies for proteins which undergo internalization in cycling, proteins that target intracellular localization and enhance intracellular half-life. The technique of receptor-mediated endocytosis is described, for example, by Wu et al., J. Biol. Chem. 262, 4429-4432 (1987); and Wagner et al., Proc. Natl. Acad. Sci. USA 87, 3410-3414 (1990). For review of gene marking and gene therapy protocols see Anderson et al., Science 256, 808-813 (1992). The Bolekine polypeptides described herein may also be employed as molecular weight markers for protein electrophoresis purposes and the isolated nucleic acid sequences may be used for recombinantly expressing those markers. The nucleic acid molecules encoding the Bolekine polypeptides or fragments thereof described herein are useful for chromosome identification. In this regard, there exists an ongoing need to identify new chromosome markers, since relatively few chromosome marking reagents, based upon actual sequence data are presently available. Each Bolekine nucleic acid molecule of the present invention can be used as a chromosome marker. The Bolekine polypeptides and nucleic acid molecules of the present invention may also be used diagnostically for tissue typing, wherein the Bolekine polypeptides of the present invention may be differentially expressed in one tissue as compared to another, preferably in a diseased tissue as compared to a normal tissue of the same tissue type. Bolekine nucleic acid molecules will find use for generating probes for PCR, Northern analysis, Southern analysis and Western analysis. The Bolekine polypeptides described herein may also be employed as therapeutic agents. The Bolekine polypeptides of the present invention can be formulated according to known methods to prepare pharmaceutically useful compositions, whereby the Bolekine product hereof is combined in admixture with a pharmaceutically acceptable carrier vehicle. Therapeutic formulations are prepared for storage by mixing the active ingredient having the desired degree of purity with optional physiologically acceptable carriers, excipients or stabilizers (Remington's Pharmaceutical Sciences 16th edition, Osol, A. Ed. (1980)), in the form of lyophilized formulations or aqueous solutions. Acceptable carriers, excipients or stabilizers are nontoxic to recipients at the dosages and concentrations employed, and include buffers such as phosphate, citrate and other organic acids; antioxidants including ascorbic acid; low molecular weight (less than about 10 residues) polypeptides; proteins, such as serum albumin, gelatin or immunoglobulins; hydrophilic polymers such as polyvinylpyrrolidone, amino acids such as glycine, glutamine, asparagine, arginine or lysine; monosaccharides, disaccharides and other carbohydrates including glucose, mannose, or dextrins; chelating agents such as EDTA; sugar alcohols such as mannitol or sorbitol; salt-forming counterions such as sodium; and/or nonionic surfactants such as TWEEN™, PLURONICS™ or PEG. The formulations to be used for in vivo aclministration must be sterile. This is readily accomplished by filtration through sterile filtration membranes, prior to or following lyophilization and reconstitution. Therapeutic compositions herein generally are placed into a container having a sterile access port, for example, an intravenous solution bag or vial having a stopper pierceable by a hypodermic injection needle. The route of administration is in accord with known methods, e.g. injection or infusion by intravenous, intraperitoneal, intracerebral, intramuscular, intraocular, intraarterial or intralesional routes, topical aclrninistration, or by sustained release systems. Dosages and desired drug concentrations of pharmaceutical compositions of the present invention may vary depending on the particular use envisioned. The determination of the appropriate dosage or route of administration is well within the skill of an ordinary physician. Animal experiments provide reliable guidance for the deteπnination of effective doses for human therapy. Interspecies scaling of effective doses can be performed following the principles laid down by Mordenti, J. and Chappell, W. "The use of interspecies scaling in toxicokinetics" In Toxicokinetics and New Drug Development, Yacobi et al., Eds., Pergamon Press, New York 1989, pp. 42-96. When in vivo administration of a Bolekine polypeptide or agonist or antagonist thereof is employed, normal dosage amounts may vary from about 10 ng/kg to up to 100 mg/kg of mammal body weight or more per day, preferably about 1 μg/kg/day to 10 mg/kg/day, depending upon the route of administration. Guidance as to particular dosages and methods of delivery is provided in the literature; see, for example, U.S. Pat. Nos. 4,657,760; 5,206,344; or 5,225,212. It is anticipated that different formulations will be effective for different treatment compounds and different disorders , that aclministration targeting one organ or tissue, for example, may necessitate delivery in a manner different from that to another organ or tissue. Where sustained-release aclministration of a Bolekine polypeptide is desired in a formulation with release characteristics suitable for the treatment of any disease or disorder requiring administration of the Bolekine polypeptide, microencapsulation of the Bolekine polypeptide is contemplated. Microencapsulation of recombinant proteins for sustained release has been successfully performed with human growth hormone (rhGH) , interferon- (rhlFN- ), interleukin-2, and MN rgpl20. Johnson et al., Nat. Med., 2:795-799 (1996); Yasuda, Biomed. Ther.. 27:1221-1223 (1993); Hora et al., Bio/Technology. 8:755-758 (1990); Cleland, "Design and Production of Single Immunization Vaccines Using Polylactide Polyglycolide Microsphere Systems, " in Vaccine Design: The Subunit and Adjuvant Approach, Powell and Newman, eds, (Plenum Press: New York, 1995), pp. 439-462; WO 97/03692, WO 96/40072, WO 96/07399; and U.S. Pat. No. 5,654,010. The sustained-release formulations of these proteins were developed using poly-lactic-coglycolic acid (PLGA) polymer due to its biocompatibility and wide range of biodegradable properties. The degradation products of PLGA, lactic and glycolic acids, can be cleared quickly within the human body. Moreover, the degradability of this polymer can be adjusted from months to years depending on its molecular weight and composition. Lewis, "Controlled release of bioactive agents from lactide/glycolide polymer," in: M. Chasin and R. Langer (Eds.), Biodegradable Polymers as Drug Delivery Systems (Marcel Dekker: New York, 1990), pp. 1-41. This invention encompasses methods of screening compounds to identify those that mimic the Bolekine polypeptide (agonists) or prevent the effect of the Bolekine polypeptide (antagonists). Screening assays for antagonist drug candidates are designed to identify compounds that bind or complex with the Bolekine polypeptides encoded by the genes identified herein, or otherwise interfere with the interaction of the encoded polypeptides with other cellular proteins. Such screening assays will include assays amenable to high-throughput screening of chemical libraries, making them particularly suitable for identifying small molecule drug candidates. The assays can be performed in a variety of formats, including protein-protein binding assays, biochemical screening assays, immunoassays, and cell-based assays, which are well characterized in the art. All assays for antagonists are common in that they call for contacting the drug candidate with a Bolekine polypeptide encoded by a nucleic acid identified herein under conditions and for a time sufficient to allow these two components to interact. In binding assays, the interaction is binding and the complex formed can be isolated or detected in the reaction mixture. In a particular embodiment, the Bolekine polypeptide encoded by the gene identified herein or the drug candidate is immobilized on a solid phase, e.g., on a microtiter plate, by covalent or non-covalent attachments. Non-covalent attachment generally is accomplished by coating the solid surface with a solution of the Bolekine polypeptide and drying. Alternatively, an immobilized antibody, e.g., a monoclonal antibody, specific for the Bolekine polypeptide to be immobilized can be used to anchor it to a solid surface. The assay is performed by adding the non-immobilized component, which may be labeled by a detectable label, to the immobilized component, e.g., the coated surface containing the anchored component. When the reaction is complete, the non-reacted components are removed, e.g., by washing, and complexes anchored on the solid surface are detected. When the originally non-immobilized component carries a detectable label, the detection of label immobilized on the surface indicates that complexing occurred. Where the originally non-immobilized component does not carry a label, complexing can be detected, for example, by using a labeled antibody specifically binding the immobilized complex. If the candidate compound interacts with but does not bind to a particular Bolekine polypeptide encoded by a gene identified herein, its interaction with that polypeptide can be assayed by methods well known for detecting protein-protein interactions. Such assays include traditional approaches, such as, e.g., cross-linking, co-immunoprecipitation, and co-purification through gradients or chromatographic columns. In addition, protein-protein interactions can be monitored by using a yeast-based genetic system described by Fields and co- workers (Fields and Song, Nature (London), 340:245-246 (1989); Chien et al., Proc. Natl. Acad. Sci. USA, 88:9578-9582 (1991)) as disclosed by Chevray and Nathans, Proc. Natl. Acad. Sci. USA. 89: 5789-5793 (1991). Many transcriptional activators, such as yeast GAL4, consist of two physically discrete modular domains, one acting as the DNA-binding domain, the other one functioning as the transcription-activation domain. The yeast expression system described in the foregoing publications (generally referred to as the "two-hybrid system") takes advantage of this property, and employs two hybrid proteins, one in which the target protein is fused to the DNA-binding domain of GAL4, and another, in which candidate activating proteins are fused to the activation domain. The expression of a GALl-tαcZ reporter gene under control of a GAL4-activated promoter depends on reconstitution of GAL4 activity via protein-protein interaction. Colonies containing interacting polypeptides are detected with a chromogenic substrate for β-galactosidase. A complete kit (MATCHMAKER™) for identifying protein-protein interactions between two specific proteins using the two- hybrid technique is commercially available from Clontech. This system can also be extended to map protein domains involved in specific protein interactions as well as to pinpoint amino acid residues that are crucial for these interactions. Compounds that interfere with the interaction of a gene encoding a Bolekine polypeptide identified herein and other intra- or extracellular components can be tested as follows: usually a reaction mixture is prepared containing the product of the gene and the intra- or extracellular component under conditions and for a time allowing for the interaction and binding of the two products. To test the ability of a candidate compound to inhibit binding, the reaction is run in the absence and in the presence of the test compound. In addition, a placebo may be added to a third reaction mixture, to serve as positive control. The binding (complex formation) between the test compound and the intra- or extracellular component present in the mixture is monitored as described hereinabove. The formation of a complex in the control reaction(s) but not in the reaction mixture containing the test compound indicates that the test compound interferes with the interaction of the test compound and its reaction partner. To assay for antagonists, the Bolekine polypeptide may be added to a cell along with the compound to be screened for a particular activity and the ability of the compound to inhibit the activity of interest in the presence of the Bolekine polypeptide indicates that the compound is an antagonist to the Bolekine polypeptide. Alternatively, antagonists may be detected by combining the Bolekine polypeptide and a potential antagonist with membrane-bound Bolekine polypeptide receptors or recombinant receptors under appropriate conditions for a competitive inhibition assay. The Bolekine polypeptide can be labeled, such as by radioactivity, such that the number of Bolekine polypeptide molecules bound to the receptor can be used to determine the effectiveness of the potential antagonist. The gene encoding the receptor can be identified by numerous methods known to those of skill in the art, for example, ligand panning and FACS sorting. Coligan et al. , Current Protocols in Immun.. 1(2): Chapter 5 (1991). Preferably, expression cloning is employed wherein polyadenylated RNA is prepared from a cell responsive to the Bolekine polypeptide and a cDNA library created from this RNA is divided into pools and used to transfect COS cells or other cells that are not responsive to the Bolekine polypeptide. Transfected cells that are grown on glass slides are exposed to labeled Bolekine polypeptide. The Bolekine polypeptide can be labeled by a variety of means including iodination or inclusion of a recognition site for a site- specific protein kinase. Following fixation and incubation, the slides are subjected to autoradiographic analysis. Positive pools are identified and sub-pools are prepared and re-transfected using an interactive sub-pooling and re-screening process, eventually yielding a single clone that encodes the putative receptor. As an alternative approach for receptor identification, labeled Bolekine polypeptide can be photoaff inity- linked with cell membrane or extract preparations that express the receptor molecule. Cross-linked material is resolved by PAGE and exposed to X-ray film. The labeled complex containing the receptor can be excised, resolved into peptide fragments, and subjected to protein micro-sequencing. The amino acid sequence obtained from micro- sequencing would be used to design a set of degenerate oligonucleotide probes to screen a cDNA library to identify the gene encoding the putative receptor. In another assay for antagonists, mammalian cells or a membrane preparation expressing the receptor would be incubated with labeled Bolekine polypeptide in the presence of the candidate compound. The ability of the compound to enhance or block this interaction could then be measured. More specific examples of potential antagonists include an oligonucleotide that binds to the fusions of immunoglobulin with Bolekine polypeptide, and, in particular, antibodies including, without limitation, poly- and monoclonal antibodies and antibody fragments, single-chain antibodies, anti-idiotypic antibodies, and ehimeric or humanized versions of such antibodies or fragments, as well as human antibodies and antibody fragments. Alternatively, a potential antagonist may be a closely related protein, for example, a mutated form of the Bolekine polypeptide that recognizes the receptor but imparts no effect, thereby competitively inhibiting the action of the Bolekine polypeptide. Another potential Bolekine polypeptide antagonist is an antisense RNA or DNA construct prepared using antisense technology, where, e.g., an antisense RNA or DΝA molecule acts to block directly the translation of mRΝA by hybridizing to targeted mRNA and preventing protein translation. Antisense technology can be used to control gene expression through triple-helix formation or antisense DΝA or RΝA, both of which methods are based on binding of a polynucleotide to DΝA or RNA. For example, the 5 ' coding portion of the polynucleotide sequence, which encodes the mature Bolekine polypeptides herein, is used to design an antisense RNA oligonucleotide of from about 10 to 40 base pairs in length. A DΝA oligonucleotide is designed to be complementary to a region of the gene involved in transcription (triple helix - see Lee et al., Νucl. Acids Res., 6:3073 (1979); Cooney et al., Science. 241: 456 (1988); Dervan et al., Science. 251:1360 (1991)), thereby preventing transcription and the production of the Bolekine polypeptide. The antisense RNA oligonucleotide hybridizes to the mRNA in vivo and blocks translation of the mRNA molecule into the Bolekine polypeptide (antisense - Okano, Νeurochem., 56:560 (1991); Oligodeoxynucleotides as Antisense Inhibitors of Gene Expression (CRC Press: Boca Raton, FL, 1988). The oligonucleotides described above can also be delivered to cells such that the antisense RΝA or DΝA may be expressed in vivo to inhibit production of the Bolekine polypeptide. When antisense DΝA is used, oligodeoxyribonucleotides derived from the translation-initiation site, e.g., between about -10 and +10 positions of the target gene nucleotide sequence, are preferred. Potential antagonists include small molecules that bind to the active site, the receptor binding site, or growth factor or other relevant binding site of the Bolekine polypeptide, thereby blocking the normal biological activity of the Bolekine polypeptide. Examples of small molecules include, but are not limited to, small peptides or peptide-like molecules, preferably soluble peptides, and synthetic non-peptidyl organic or inorganic compounds. Ribozymes are enzymatic RΝA molecules capable of catalyzing the specific cleavage of RΝA. Ribozymes act by sequence-specific hybridization to the complementary target RΝA, followed by endonucleolytic cleavage. Specific ribozyme cleavage sites within a potential RΝA target can be identified by known techniques. For further details see, e.g., Rossi, Current Biology, 4:469-471 (1994), and PCT publication No. WO 97/33551 (published September 18, 1997). Nucleic acid molecules in triple-helix formation used to inhibit transcription should be single-stranded and composed of deoxynucleotides. The base composition of these oligonucleotides is designed such that it promotes triple-helix formation via Hoogsteen base-pairing rules, which generally require sizeable stretches of purines or pyrimidines on one strand of a duplex. For further details see, e.g., PCT publication No. WO 97/33551, supra. These small molecules can be identified by any one or more of the screening assays discussed hereinabove and/or by any other screening techniques well known for those skilled in the art. Diagnostic and therapeutic uses of the herein disclosed molecules may also be based upon the positive functional assay hits disclosed and described below. As chemokines that lack the ELR motif such as Bolekine, are angiostatic (Strieter RM. et al. Journal of Biological Chemistry 1995; 270: 27348-27357), then Bolekine may be useful in treating tumors by inhibiting the neovascularization that accompanies tumor growth. Admistration of the Bolekine polypeptide either alone or in combination with another angiostatic factor such as anti-VEGF, may prove useful in limiting or reducing tumor growth. Chemokines may be able to activate immune cells, as shown with the CXC chemokines activation of neutrophils (Baggiolini et al. Adv Immunology 1994; 55:97-179), and the non-CXC chemokines are mainly chemotactic for T lymphocytes. Bolekine may be useful in treating infection, as local administration of the polypeptide would stimulate immune cells already present at the site of infection and induce more immune cells to migrate to the site, thus removing the infection at a faster rate. F. Anti-Bolekine Antibodies The present invention further provides anti-Bolekine antibodies. Exemplary antibodies include polyclonal, monoclonal, humanized, bispecific, and heteroconjugate antibodies. 1. Polyclonal Antibodies The anti-Bolekine antibodies may comprise polyclonal antibodies. Methods of preparing polyclonal antibodies are known to the skilled artisan. Polyclonal antibodies can be raised in a mammal, for example, by one or more injections of an immunizing agent and, if desired, an adjuvant. Typically, the immunizing agent and/or adjuvant will be injected in the mammal by multiple subcutaneous or intraperitoneal injections. The immunizing agent may include the Bolekine polypeptide or a fusion protein thereof. It may be useful to conjugate the immunizing agent to a protein known to be immunogenic in the mammal being immunized. Examples of such immunogenic proteins include but are not limited to keyhole limpet hemocyanin, serum albumin, bovine thyroglobulin, and soybean trypsin inhibitor. Examples of adjuvants which may be employed include Freund's complete adjuvant and MPL-TDM adjuvant (monophosphoryl Lipid A, synthetic trehalose dicorynomycolate). The immunization protocol may be selected by one skilled in the art without undue experimentation. 2. Monoclonal Antibodies The anti-Bolekine antibodies may, alternatively, be monoclonal antibodies. Monoclonal antibodies may be prepared using hybridoma methods, such as those described by Kohler and Milstein, Nature.256:495 (1975). In a hybridoma method, a mouse, hamster, or other appropriate host animal, is typically immunized with an immunizing agent to elicit lymphocytes that produce or are capable of producing antibodies that will specifically bind to the immunizing agent. Alternatively, the lymphocytes may be immunized in vitro. The immunizing agent will typically include the Bolekine polypeptide or a fusion protein thereof. Generally, either peripheral blood lymphocytes ("PBLs") are used if cells of human origin are desired, or spleen cells or lymph node cells are used if non-human mammalian sources are desired. The lymphocytes are then fused with an immortalized cell line using a suitable fusing agent, such as polyethylene glycol, to form a hybridoma cell [Goding, Monoclonal Antibodies: Principles and Practice, Academic Press, (1986) pp. 59-103] . Immortalized cell lines are usually transformed mammalian cells, particularly myeloma cells of rodent, bovine and human origin. Usually, rat or mouse myeloma cell lines are employed. The hybridoma cells may be cultured in a suitable culture medium that preferably contains one or more substances that inhibit the growth or survival of the unfused, immortalized cells. For example, if the parental cells lack the enzyme hypoxanthine guanine phosphoribosyl transferase (HGPRT or HPRT), the culture medium for the hybridomas typically will include hypoxanthine, aminopterin, and thymidine ("HAT medium"), which substances prevent the growth of HGPRT-deficient cells. Preferred immortalized cell lines are those that fuse efficiently, support stable high level expression of antibody by the selected antibody-producing cells, and are sensitive to a medium such as HAT medium. More preferred immortalized cell lines are murine myeloma lines, which can be obtained, for instance, from the Satk Institute Cell Distribution Center, San Diego, California and the American Type Culture Collection, Manassas, Virginia. Human myeloma and mouse-human heteromyeloma cell lines also have been described for the production of human monoclonal antibodies [Kozbor, J. Immunol., 133:3001 (1984); Brodeur etal., Monoclonal Antibody Production Techniques and Applications, Marcel Dekker, Inc., New York, (1987) pp. 51-63]. The culture medium in which the hybridoma cells are cultured can then be assayed for the presence of monoclonal antibodies directed against Bolekine. Preferably, the binding specificity of monoclonal antibodies produced by the hybridoma cells is determined by immunoprecipitation or by an in vitro binding assay; such as radioimmunoassay (RIA) or enzyme-linked immunoabsorbent assay (ELISA). Such techniques and assays are known in the art. The binding affinity of the monoclonal antibody can, for example, be determined by the Scatchard analysis of Munson and Pollard, Anal. Biochem., .107:220 (1980). After the desired hybridoma cells are identified, the clones may be subcloned by limiting dilution procedures and grown by standard methods [Goding, supra] . Suitable culture media for this purpose include, for example, Dulbecco's Modified Eagle's Medium and RPMI-1640 medium. Alternatively, the hybridoma cells may be grown in vivo as ascites in a mammal. The monoclonal antibodies secreted by the subclones may be isolated or purified from the culture medium or ascites fluid by conventional immunoglobulin purification procedures such as, for example, protein A-Sepharose, hydroxylapatite chromatography, gel electrophoresis, dialysis, or affinity chromatography. The monoclonal antibodies may also be made by recombinant DNA methods, such as those described in U.S. PatentNo. 4,816,567. DNA encoding the monoclonal antibodies of the invention can be readily isolated and sequenced using conventional procedures (e.g., by using oligonucleotide probes that are capable of binding specifically to genes encoding the heavy and light chains of murine antibodies). The hybridoma cells of the invention serve as a preferred source of such DNA. Once isolated, the DNA may be placed into expression vectors, which are then transfected into host cells such as simian COS cells, Chinese hamster ovary (CHO) cells, or myeloma cells that do not otherwise produce immunoglobulin protein, to obtain the synthesis of monoclonal antibodies in the recombinant host cells. The DNA also may be modified, for example, by substituting the coding sequence for human heavy and light chain constant domains in place of the homologous murine sequences [U.S. Patent No. 4,816,567; Morrison et al., supra] or by covalently joining to the immunoglobulin coding sequence all or part of the coding sequence for a non-immunoglobulin polypeptide. Such a non-immunoglobulin polypeptide can be substituted for the constant domains of an antibody of the invention, or can be substituted for the variable domains of one antigen-combining site of an antibody of the invention to create a ehimeric bivalent antibody. The antibodies may be monovalent antibodies. Methods for preparing monovalent antibodies are well known in the art. For example, one method involves recombinant expression of immunoglobulin light chain and modified heavy chain. The heavy chain is truncated generally at any point in the Fc region so as to prevent heavy chain crosslinking. Alternatively, the relevant cysteine residues are substituted with another amino acid residue or are deleted so as to prevent crosslinking. In vitro methods are also suitable for preparing monovalent antibodies. Digestion of antibodies to produce fragments thereof, particularly, Fab fragments, can be accomplished using routine techniques known in the art. 3. Human and Humanized Antibodies The anti-Bolekine antibodies of the invention may further comprise humanized antibodies or human antibodies. Humanized forms of non-human (e.g., murine) antibodies are ehimeric immunoglobulins, immunoglobulin chains or fragments thereof (such as Fv, Fab, Fab', F(ab') 2 or other antigen-binding subsequences of antibodies) which contain minimal sequence derived from non-human immunoglobulin. Humanized antibodies include human immunoglobulins (recipient antibody) in which residues from a complementary determining region (CDR) of the recipient are replaced by residues from a CDR of a non-human species (donor antibody) such as mouse, rat or rabbit having the desired specificity, affinity and capacity. In some instances, Fv framework residues of the human immunoglobulin are replaced by corresponding non-human residues. Humanized antibodies may also comprise residues which are found neither in the recipient antibody nor in the imported CDR or framework sequences. In general, the humanized antibody will comprise substantially all of at least one, and typically two, variable domains, in which all or substantially all of the CDR regions correspond to those of a non-human immunoglobulin and all or substantially all of the FR regions are those of a human immunoglobulin consensus sequence. The humanized antibody optimally also will comprise at least a portion of an immunoglobulin constant region (Fc), typically that of a human immunoglobulin [Jones et al., Nature. 321:522-525 (1986); Riechmann et al., Nature. 332:323-329 (1988); and Presta, Curr. Op. Struct. Biol.. 2:593-596 (1992)]. Methods for humanizing non-human antibodies are well known in the art. Generally, a humanized antibody has one or more amino acid residues introduced into it from a source which is non-human. These non- human amino acid residues are often referred to as "import" residues, which are typically taken from an "import" variable domain. Humanization can be essentially performed following the method of Winter and co- workers [Jones et al., Nature. 321:522-525 (1986); Riechmann et al., Nature, 332:323-327 (1988); Verhoeyen et al., Science. 239:1534-1536 (1988)], by substituting rodent CDRs or CDR sequences for the corresponding sequences of ahuman antibody. Accordingly, such "humanized" antibodies are ehimeric antibodies (U.S. Patent No. 4,816,567), wherein substantially less than an intact human variable domain has been substituted by the corresponding sequence from a non-human species. In practice, humanized antibodies are typically human antibodies in which some CDR residues and possibly some FR residues are substituted by residues from analogous sites in rodent antibodies. Human antibodies can also be produced using various techniques known in the art, including phage display libraries [Hoogenboom and Winter, J. Mol. Biol.. 227:381 (1991); Marks et al., J. Mol. Biol.. 222:581 (1991)]. The techniques of Cole et al. and Boerner et al. are also available for the preparation of human monoclonal antibodies (Cole et al., Monoclonal Antibodies and Cancer Therapy. AlanR. Liss, p. 77 (1985) and Boerner et al., J. Immunol.. 147(l):86-95 (1991)]. Similarly, human antibodies can be made by introducing of human immunoglobulin loci into transgenic animals, e.g., mice in which the endogenous immunoglobulin genes have been partially or completely inactivated. Upon challenge, human antibody production is observed, which closely resembles that seen in humans in all respects, including gene rearrangement, assembly, and antibody repertoire. This approach is described, for example, in U.S. Patent Nos. 5,545,807; 5,545,806; 5,569,825; 5,625,126; 5,633,425; 5,661,016, and in the following scientific publications: Marks et al, Bio/Technology 10, 779-783 (1992); Lonbergetflt., Nature 368856-859 (1994); Morrison, Nature 368. 812-13 (1994); Fishwild et al., Nature Biotechnology 14, 845-51 (1996); Neuberger, Nature Biotechnology 14, 826 (1996); Lonberg and Huszar, Intern. Rev. Immunol. 13 65-93 (1995). The antibodies may also be affinity matured using known selection and/or mutagenesis methods as described above. Preferred affinity matured antibodies have an affinity which is five times, more preferably 10 times, even more preferably 20 or 30 times greater than the starting antibody (generally murine, humanized or human) from which the matured antibody is prepared. 4. Bispecific Antibodies Bispecific antibodies are monoclonal, preferably human or humanized, antibodies that have binding specificities for at least two different antigens. In the present case, one of the binding specificities is for the Bolekine, the other one is for any other antigen, and preferably for a cell-surface protein or receptor or receptor subunit. Methods for making bispecific antibodies are known in the art. Traditionally, the recombinant production of bispecific antibodies is based on the co-expression of two immunoglobulin heavy-chain/light-chain pairs, where the two heavy chains have different specificities [Milstein and Cuello, Nature, 305:537-539 (1983)]. Because of the random assortment of immunoglobulin heavy and light chains, these hybridomas (quadromas) produce a potential mixture of ten different antibody molecules, of which only one has the correct bispecific structure. The purification of the correct molecule is usually accomplished by affinity chromatography steps. Similar procedures are disclosed in WO 93/08829, published 13 May 1993, and in Traunecker et al., EMBO , 10:3655-3659 (1991). Antibody variable domains with the desired binding specificities (antibody-antigen combining sites) can be fused to immunoglobulin constant domain sequences. The fusion preferably is with an immunoglobulin heavy-chain constant domain, comprising at least part of the hinge, CH2, and CH3 regions. It is preferred to have the first heavy-chain constant region (CHI) containing the site necessary for light-chain binding present in at least one of the fusions. DNAs encoding the immunoglobulin heavy-chain fusions and, if desired, the immunoglobulin light chain, are inserted into separate expression vectors, and are co-transfected into a suitable host organism. For further details of generating bispecific antibodies see, for example, Suresh et al. , Methods in Enzymology, 121:210 (1986). According to another approach described in WO 96/27011, the interface between a pair of antibody molecules can be engineered to maximize the percentage of heterodimers which are recovered from recombinant cell culture . The preferred interface comprises at least a part of the CH3 region of an antibody constant domain. In this method, one or more small amino acid side chains from the interface of the first antibody molecule are replaced with larger side chains (e.g. tyrosine or tryptophan). Compensatory "cavities" of identical or similar size to the large side chain(s) are created on the interface of the second antibody molecule by replacing large amino acid side chains with smaller ones (e.g. alanine or threonine). This provides a mechanism for increasing the yield of the heterodimer over other unwanted end-products such as homodimers. Bispecific antibodies can be prepared as full length antibodies or antibody fragments (e.g. F(ab') 2 bispecific antibodies). Techniques for generating bispecific antibodies from antibody fragments have been described in the literature. For example, bispecific antibodies can be prepared can be prepared using chemical linkage. Brennan et al. , Science 229 :81 (1985) describe a procedure wherein intact antibodies are proteolytically cleaved to generate F(ab') 2 fragments. These fragments are reduced in the presence of the dithiol complexing agent sodium arsenite to stabilize vicinal dithiols and prevent intermolecular disulfide formation. The Fab' fragments generated are then converted to thionitrobenzoate (TNB) derivatives. One of the Fab'-TNB derivatives is then reconverted to the Fab'-thiol by reduction with mercaptoethylamine and is mixed with an equimolar amount of the other Fab'-TNB derivative to form the bispecific antibody. The bispecific antibodies produced can be used as agents for the selective immobilization of enzymes. Fab' fragments may be directly recovered from E. coli and chemically coupled to form bispecific antibodies. Shalaby et al., J. Exp. Med. 175:217-225 (1992) describe the production of a fully humanized bispecific antibody F(ab') 2 molecule. Each Fab' fragment was separately secreted from E. coli and subjected to directed chemical coupling in vitro to form the bispecific antibody. The bispecific antibody thus formed was able to bind to cells overexpressing the ErbB2 receptor and normal human T cells, as well as trigger the lytic activity of human cytotoxic lymphocytes against human breast tumor targets. Various technique for making and isolating bispecific antibody fragments directly from recombinant cell culture have also been described. For example, bispecific antibodies have been produced using leucine zippers . Kostelny et al., J. Immunol. 148(5): 1547-1553 (1992). The leucine zipper peptides from the Fos and Jun proteins were linked to the Fab' portions of two different antibodies by gene fusion. The antibody homodimers were reduced at the hinge region to form monomers and then re-oxidized to form the antibody heterodimers. This method can also be utilized for the production of antibody homodimers. The "diabody" technology described by Hollinger et al., Proc. Natl. Acad. Sci. USA 90:6444-6448 (1993) has provided an alternative mechanism for making bispecific antibody fragments. The fragments comprise a heavy-chain variable domain (V H ) connected to a light-chain variable domain (V L ) by a linker which is too short to allow pairing between the two domains on the same chain. Accordingly, the V H and V L domains of one fragment are forced to pair with the complementary V L and V H domains of another fragment, thereby forming two antigen-binding sites . Another strategy for making bispecific antibody fragments by the use of single-chain Fv (sFv) dimers has also been reported. See, Gruber et al., J. Immunol. 152:5368 (1994). Antibodies with more than two valencies are contemplated. For example, trispecific antibodies can be prepared. Tutt et al. , J. Immunol. 147:60 (1991). Exemplary bispecific antibodies may bind to two different epitopes on a given Bolekine polypeptide herein. Alternatively, an anti-Bolekine polypeptide arm may be combined with an arm which binds to a triggering molecule on a leukocyte such as a T-cell receptor molecule (e.g. CD2, CD3, CD28, or B7), or Fc receptors for IgG (FcγR), such as FcγRI (CD64), FcγRlI (CD32) and FcγRITI (CD16) so as to focus cellular defense mechanisms to the cell expressing the particular Bolekine polypeptide. Bispecific antibodies may also be used to localize cytotoxic agents to cells which express a particular Bolekine polypeptide. These antibodies possess a Bolekine-binding arm and an arm which binds a cytotoxic agent or a radionuclide chelator, such as EOTUBE, DPTA, DOTA, or TETA. Another bispecific antibody of interest binds the Bolekine polypeptide and further binds tissue factor (TF). 5. Heteroconiugate Antibodies Heteroconjugate antibodies are also within the scope of the present invention. Heteroconjugate antibodies are composed of two covalently joined antibodies. Such antibodies have, for example, been proposed to target immune system cells to unwanted cells [U.S. Patent No.4,676,980], and for treatment of HIV infection [WO 91/00360; WO 92/200373; EP 03089]. It is contemplated that the antibodies may be prepared in vitro using known methods in synthetic protein chemistry, including those involving crosslinking agents. For example, immunotoxins may be constructed using a disulfide exchange reaction or by forming a thioether bond. Examples of suitable reagents for this purpose include iminothiolate and methyl-4-mercaptobutyrirnidate and those disclosed, for example, in U.S. Patent No. 4,676,980. 6. Effector Function Engineering It may be desirable to modify the antibody of the invention with respect to effector function, so as to enhance, e.g., the effectiveness of the antibody in treating cancer. For example, cysteine residue(s) may be introduced into the Fc region, thereby allowing interchain disulfide bond formation in this region. The homodimeric antibody thus generated may have improved internalization capability and/or increased complement-mediated cell killing and antibody-dependent cellular cytotoxicity (ADCC). See Caron et al. , Exp Med., 176: 1191-1195 (1992) and Shopes, J. Immunol., 148: 2918-2922 (1992). Homodimeric antibodies with enhanced anti-tumor activity may also be prepared using heterobifunctional cross-linkers as described in Wolff et al. Cancer Research. 53 : 2560-2565 (1993). Alternatively, an antibody can be engineered that has dual Fc regions and may thereby have enhanced complement lysis and ADCC capabilities. See Stevenson et al, Anti-Cancer Drug Design. 3: 219-230 (1989). 7. Immunoconiugates The invention also pertains to immunoconjugates comprising an antibody conjugated to a cytotoxic agent such as a chemotherapeutic agent, toxin (e.g. , an enzymatically active toxin of bacterial, fungal, plant, or animal origin, or fragments thereof), or a radioactive isotope (i.e., a radioconjugate). Chemotherapeutic agents useful in the generation of such immunoconjugates have been described above . Enzymatically active toxins and fragments thereof that can be used include diphtheria A chain, nonbinding active fragments of diphtheria toxin, exotoxin A chain (from Pseudomonas aeruginosa), ricin A chain, abrin A chain, modeccin A chain, alpha-sarcin, Aleurites fordii proteins, dianthin proteins, Phytolaca americana proteins (PAPI, PAPH, and PAP-S), momordica charantia inhibitor, curcin, crotin, sapaonaria officinalis inhibitor, gelonin, mitogellin, restrictocin, phenomycin, enomycin, and the tricothecenes. A variety of radionuclides are available for the production of radioconjugated antibodies. Examples include 212 Bi, 131 I, 131 Lι, 90 Y, and 186 Re. Conjugates of the antibody and cytotoxic agent are made using a variety of bifunctional protein-coupling agents such as N-succinimidyl-3-(2-pyridyldifhiol) propionate (SPDP), iminothiolane (IT), bifunctional derivatives of imidoesters (such as dimethyl adipimidate HCL), active esters (such as disuccinimidyl suberate), aldehydes (such as glutareldehyde), bis-azido compounds (such as bis (p-azidobenzoyl) hexanediamine), bis- diazonium derivatives (such as bis-(p-diazomumbenzoyl)-ethylenediamine), diisocyanates (such as tolyene 2,6- diisocyanate), and bis-active fluorine compounds (such as l,5-difluoro-2,4-dinitrobenzene). For example, aricin immunotoxin can be prepared as described in Vitetta et al. , Science, 238: 1098 (1987). Carbon- 14-labeled 1- isothiocyanatobenzyl-3-methyldiethylene triaminepentaacetic acid (MX-DTPA) is an exemplary chelating agent for conjugation of radionucleotide to the antibody. See W094/11026. In another embodiment, the antibody may be conjugated to a "receptor" (such streptavidin) for utilization in tumor pretargeting wherein the antibody-receptor conjugate is administered to the patient, followed by removal of unbound conjugate from the circulation using a clearing agent and then administration of a "ligand" (e.g., avidin) that is conjugated to a cytotoxic agent (e.g., a radionucleotide). 8. Immunoliposomes The antibodies disclosed herein may also be formulated as immunoliposomes. Liposomes containing the antibody are prepared by methods known in the art, such as described in Epstein et ah, Proc. Natl. Acad. Sci. USA. 82: 3688 (1985); Hwang et al, Proc. Natl Acad. Sci. USA. 77: 4030 (1980); and U.S. Pat. Nos. 4,485,045 and 4,544,545. Liposomes with enhanced circulation time are disclosed in U.S. Patent No. 5,013,556. Particularly useful liposomes can be generated by the reverse-phase evaporation method with a lipid composition comprising phosphatidylcholine, cholesterol, andPEG-derivatizedphosphatidylethanolamine (PEG- PE). Liposomes are extruded through filters of defined pore size to yield liposomes with the desired diameter. Fab' fragments of the antibody of the present invention can be conjugated to the liposomes as described in Martin et al .. J. Biol. Chem., 257: 286-288 (1982) via a disulfide-interchange reaction. A chemotherapeutic agent (such as Doxorubicin) is optionally contained within the liposome. See Gabizon et al. , J. National Cancer List.. 81(19): 1484 (1989). 9. Pharmaceutical Compositions of Antibodies Antibodies specifically binding a Bolekine polypeptide identified herein, as well as other molecules identified by the screening assays disclosed hereinbefore, can be administered for the treatment of various disorders in the form of pharmaceutical compositions. If the Bolekine polypeptide is intracellular and whole antibodies are used as inhibitors, internalizing antibodies are preferred. However, lipofections or liposomes can also be used to deliver the antibody, or an antibody fragment, into cells. Where antibody fragments are used, the smallest inhibitory fragment that specifically binds to the binding domain of the target protein is preferred. For example, based upon the variable- region sequences of an antibody, peptide molecules can be designed that retain the ability to bind the target protein sequence. Such peptides can be synthesized chemically and/or produced by recombinant DNA technology. See, e.g., Marasco et al, Proc. Natl. Acad. Sci. USA. 90: 7889-7893 (1993). The formulation herein may also contain more than one active compound as necessary for the particular indication being treated, preferably those with complementary activities that do not adversely affect each other. Alternatively, or in addition, the composition may comprise an agent that enhances its function, such as, for example, a cytotoxic agent, cytokine, chemotherapeutic agent, or growth-inhibitory agent. Such molecules are suitably present in combination in amounts that are effective for the purpose intended. The active ingredients may also be entrapped in microcapsules prepared, for example, by coacervation techniques or by interfacial polymerization, for example, hydroxyme hylcellulose or gelatin-microcapsules and poly-(methylmethacylate) microcapsules, respectively, in colloidal drug delivery systems (for example, liposomes, albumin microspheres, microemulsions, nano-particles, and nanocapsules) or in macroemulsions. Such techniques are disclosed in Remington's Pharmaceutical Sciences, supra. The formulations to be used for in vivo administration must be sterile. This is readily accomplished by filtration through sterile filtration membranes. Sustained-release preparations may be prepared. Suitable examples of sustained-release preparations include semipermeable matrices of solid hydrophobic polymers containing the antibody, which matrices are in the form of shaped articles, e.g., films, or microcapsules. Examples of sustained-release matrices include polyesters, hydrogels (for example, poly(2-hydroxyethyl-methacrylate), or poly(vinylalcohol)), polylactides (U.S. Pat. No. 3,773,919), copolymers of L-glutamic acid and γ ethyl-L-glutamate, non-degradable ethylene- vinyl acetate, degradable lactic acid-glycolic acid copolymers such as the LUBolekineN DEPOT ™ (injectable microspheres composed of lactic acid-glycolic acid copolymer and leuprolide acetate), and poly-D-(-)-3- hydroxybutyric acid. While polymers such as ethylene-vinyl acetate and lactic acid-glycolic acid enable release of molecules for over 100 days , certain hydrogels release proteins for shorter time periods . When encapsulated antibodies remain in the body for a long time, they may denature or aggregate as a result of exposure to moisture at 37°C, resulting in a loss of biological activity and possible changes in immunogenicity. Rational strategies can be devised for stabilization depending on the mechanism involved. For example, if the aggregation mechanism is discovered to be intermolecular S-S bond formation through thio-disulfide interchange, stabilization may be achieved by modifying sulfhydryl residues, lyophilizing from acidic solutions, controlling moisture content, using appropriate additives, and developing specific polymer matrix compositions. G. Uses for anti-Bolekine Antibodies The anti-Bolekine antibodies of the invention have various utilities. For example, anti-Bolekine antibodies may be used in diagnostic assays for Bolekine, e.g. , detecting its expression (and in some cases, differential expression) in specific cells, tissues, or serum. Various diagnostic assay techniques known in the art may be used, such as competitive binding assays, direct or indirect sandwich assays and immunoprecipitation assays conducted in either heterogeneous or homogeneous phases [Zola, Monoclonal Antibodies: A Manual of Techniques, CRC Press, Inc. (1987) pp. 147-158]. The antibodies used in the diagnostic assays can be labeled with a detectable moiety. The detectable moiety should be capable of producing, either directly or indirectly, a detectable signal. For example, the detectable moiety may be a radioisotope, such as 3 H, 14 C, 32 P, 35 S, or 125 I, a fluorescent or cherniluminescent compound, such as fluorescein isothiocyanate, rhodamine, or luciferin, or an enzyme, such as alkaline phosphatase, beta-galactosidase or horseradish peroxidase. Any method known in the art for conjugating the antibody to the detectable moiety may be employed, including those methods described by Hunter et al., Nature, 144:945 (1962); David et al., Biochemistry, .13:1014 (1974); Painet al.. J. Immunol. Meth.. 40:219 (1981); and Nygren, J. Histochem. and Cvtochem., 30:407 (1982). Anti-Bolekine antibodies also are useful for the affinity purification of Bolekine from recombinant cell culture or natural sources . In this process, the antibodies against Bolekine are immobilized on a suitable support, such a Sephadex resin or filter paper, using methods well known in the art. The immobilized antibody then is contacted with a sample containing the Bolekine to be purified, and thereafter the support is washed with a suitable solvent that will remove substantially all the material in the sample except the Bolekine, which is bound to the immobilized antibody. Finally, the support is washed with another suitable solvent that will release the Bolekine from the antibody. The following examples are offered for illustrative purposes only, and are not intended to limit the scope of the present invention in any way. All patent and literature references cited in the present specification are hereby incorporated by reference in their entirety. EXAMPLES Commercially available reagents referred to in the examples were used according to manufacturer's instructions unless otherwise indicated. The source of those cells identified in the following examples, and throughout the specification, by ATCC accession numbers is the American Type Culture Collection, Manassas, VA. EXAMPLE 1: Isolation of cDNA Clones Encoding Human Bolekine The extracellular domain (ECD) sequences (including the secretion signal, if any) of from about 950 known secreted proteins from the Swiss-Prot public protein database were used to search expressed sequence tag (EST) databases. The EST databases included public EST databases (e.g. , GenBank) and a proprietary EST DNA database (LIFESEQ^M^ incyte Pharmaceuticals, Palo Alto, CA). The search was performed using the computer program BLAST or BLAST2 (Altshul et al., Methods in Enzvmology 266:460-480 (1996)) as a comparison of the ECD protein sequences to a 6 frame translation of the EST sequence. Those comparisons resulting in a BLAST score of 70 (or in some cases 90) or greater that did not encode known proteins were clustered and assembled into consensus DNA sequences with the program "phrap" (Phil Green, University of Washington, Seattle, Washington; http://bozeman.mbt.waslu igton.edu/phrap.docs/phrap.htiril). A consensus DNA sequence was assembled relative to other EST sequences using phrap. Based on the consensus sequence, oligonucleotides were synthesized: 1) to identify by PCR a cDNA library that contained the sequence of interest, and 2) for use as probes to isolate a clone of the full-length coding sequence for Bolekine.. Forward and reverse PCR primers generally range from 20 to 30 nucleotides and are often designed to give a PCR product of about 100-1000 bp in length. The probe sequences are typically 40-55 bp in length. In some cases, additional oligonucleotides are synthesized when the consensus sequence is greater than about 1-1.5kbp. hi order to screen several libraries for a full-length clone, DNA from the libraries was screened by PCR amplification, as per Ausubel et al. , Current Protocols in Molecular Biology, with the PCR primer pair. A positive library was then used to isolate clones encoding the gene of interest by the in vivo cloning procedure using the probe oligonucleotide and one of the primer pairs. A pair of PCR primers (forward and reverse) were synthesized: forward PCR primer: 5'-CAGCGCCCTCCCCATGTCCCTG-3' (SEQ ID NO: 3) reverse PCR primer: 5'-TCCCAACTGGTTTGGAGTTTTCCC-3 ' (SEQ ID NO: 4) Additionally , a synthetic oligonucleotide hybridization probe was constructed from the consensus sequence which had the following nucleotide sequence. hybridization probe 5'-CTCCGGTCAGCATGAGGCTCCTGGCGGCCGCTGCTCCTGCTGCTG-3' (SEQ ID NO:5) In order to screen several libraries for a source of a full-length clone, DNA from the libraries was screened by PCR amplification with the PCR primer pair identified above. A positive library was then used to isolate clones encoding the Bolekine gene using the probe oligonucleotide and one of the PCR primers. RNA for construction of the cDNA libraries was isolated from human fetal kidney tissue. The cDNA libraries used to isolate the cDNA clones were constructed by standard methods using commercially available reagents such as those from Invitrogen, San Diego, CA. The cDNA was primed with oligo dT containing a Notl site, linked with blunt to Sail hemikinased adaptors, cleaved with Notl, sized appropriately by gel electrophoresis, and cloned in a defined orientation into a suitable cloning vector (such as pRKB or pRKD; pRK5B is a precursor of pRK5D that does not contain the Sfil site; see, Holmes et al., Science, 253:1278-1280 (1991)) in the unique Xhol and Notl sites. DNA sequencing of the clones isolated as described above gave the full-length DNA sequence for Bolekine (SEQ ID NO:l) and the derived protein sequence for Bolekine. The entire nucleotide sequence of Bolekine is shown in Figure 1 (SEQ ID NO:l). The Bolekine sequence contains a single open reading frame with an apparent translational initiation site at nucleotide positions 167-169 [Kozak et al., supra] and ending at the stop codon at nucleotide positions 500-502 (Figure 1). The predicted polypeptide precursor is 111 amino acids long (Figure 2 (SEQ ID NO:2)). Bolekine has been deposited with the ATCC. It is understood that the deposited clone contains the actual sequence and that the sequences provided herein are merely representative based on current sequencing techniques. Moreover, given the sequences provided herein and knowledge of the universal genetic code, the corresponding nucleotides for any given amino acid can be routinely identified and vice versa. Analysis of the amino acid sequence of the full-length Bolekine polypeptide suggests that portions of it possess sequence identity with human macrophage inflammatory protein-2, cytokine-induced neutrophil chemoattractant 2, and neutrophil chemotactic factor 2-beta, thereby indicating that Bolekine is a novel chemokine. As discussed further below, the cDNA was subcloned into a baculovirus vector and expressed in insect cells as a C-terminally tagged IgG fusion protein. N-terminal sequencing of the resultant protein identified the signal sequence cleavage site, yielding a mature polypeptide of 77 amino acids. The mature sequence, showing 31-40% identity to other human CXC chemokines, includes the four canonical cysteine residues but lacks the ELR motif. EXAMPLE 2: Use of Bolekine-encoding DNA as a hybridization probe The following method describes use of a nucleotide sequence encoding Bolekine as a hybridization probe. DNA comprising the coding sequence of full-length Bolekine (as shown in Figure 1, SEQ ID NO:l) is employed as a probe to screen for homologous DNAs (such as those encoding naturally-occurring variants of Bolekine) in human tissue cDNA libraries or human tissue genomic libraries. Hybridization and washing of filters containing either library DNAs is performed under the following high stringency conditions. Hybridization of radiolabeled Bolekine-derived probe to the filters is performed in a solution of 50% formamide, 5xSSC, 0.1% SDS, 0.1% sodium pyrophosphate, 50 mM sodium phosphate, pH 6.8, 2x Denhardt's solution, and 10% dextran sulfate at 42°C for 20 hours. Washing of the filters is performed in an aqueous solution of 0.1 x SSC and 0.1 % SDS at 42°C. DNAs having a desired sequence identity with the DNA encoding full-length native sequence Bolekine polypeptide can then be identified using standard techniques known in the art. EXAMPLE 3: Expression of Bolekine Polypeptides in E. coli This example illustrates the preparation of unglycosylated forms of Bolekine polypeptides by recombinant expression in E. coli. The DNA sequence encoding Bolekine (SEQ ID NO:l) is initially amplified using selected PCR primers. The primers should contain restriction enzyme sites which correspond to the restriction enzyme sites on the selected expression vector. A variety of expression vectors may be employed. An example of a suitable vector is pBR322 (derived from E. coli; see Bolivar et al., Gene. 2 :95 (1977)) which contains genes for ampicillin and tetracycline resistance. The vector is digested with restriction enzyme and dephosphorylated. The PCR amplified sequences are then ligated into the vector. The vector will preferably include sequences which encode for an antibiotic resistance gene, a tip promoter, a polyhis leader (including the first six STII codons, polyhis sequence, and enterokinase cleavage site), the Bolekine coding region, lambda transcriptional terminator, and an argU gene. The ligation mixture is then used to transform a selected E. coli strain using the methods described in Sambrook et al. , supra. Transformants are identified by their ability to grow on LB plates and antibiotic resistant colonies are then selected. Plasmid DNA can be isolated and confirmed by restriction analysis and DNA sequencing. Selected clones can be grown overnight in liquid culture medium such as LB broth supplemented with antibiotics. The overnight culture may subsequently be used to inoculate a larger scale culture. The cells are then grown to a desired optical density, during which the expression promoter is turned on. After culturing the cells for several more hours, the cells can be harvested by centrifugation. The cell pellet obtained by the centrifugation can be solubilized using various agents known in the art, and the solubilized Bolekine polypeptide can then be purified using a metal chelating column under conditions that allow tight binding of the polypeptide. EXAMPLE 4: Expression of Bolekine Polypeptides in Mammalian Cells This example illustrates preparation of glycosylated forms of Bolekine polypeptides by recombinant expression in mammalian cells. The vector, pRK5 (see EP 307,247, published March 15, 1989), is employed as the expression vector. Optionally, the Bolekine-encoding DNA is ligated into pRK5 with selected restriction enzymes to allow insertion of the Bolekine-encoding DNA using ligation methods such as described in Sambrook et al., supra. The resulting vector is called pRK5-Bolekine. In one embodiment, the selected host cells may be 293 cells. Human 293 cells (ATCC CCL 1573) are grown to confluence in tissue culture plates in medium such as DMEM supplemented with fetal calf serum and optionally, nutrient components and/or antibiotics. About 10 μg pRK5-Bolekine DNA is mixed with about 1 μg DNA encoding the VA RNA gene [Thimmappaya et al., Cell, 3J. :543 (1982)] and dissolved in 500 μl of 1 mM Tris-HCl, 0.1 mM EDTA, 0.227 M CaCl 2 . To this mixture is added, dropwise, 500 μl of 50 mM HEPES (pH 7.35), 280 mM NaCl, 1.5 mM NaPO and a precipitate is allowed to form for 10 minutes at 25°C. The precipitate is suspended and added to the 293 cells and allowed to settle for about four hours at 37°C. The culture medium is aspirated off and 2 ml of 20% glycerol in PBS is added for 30 seconds. The 293 cells are then washed with serum free medium, fresh medium is added and the cells are incubated for about 5 days. Approximately 24 hours after the transfections, the culture medium is removed and replaced with culture medium (alone) or culture medium containing 200 μCi/ml -"S-cysteine and 200 μd/ l 35s_ me thionine. After a 12 hour incubation, the conditioned medium is collected, concentrated on a spin filter, and loaded onto a 15% SDS gel. The processed gel may be dried and exposed to film for a selected period of time to reveal the presence of Bolekine polypeptide. The cultures containing transfected cells may undergo further incubation (in serum free medium) and the medium is tested in selected bioassays. In an alternative technique, Bolekine-encoding DNA may be introduced into 293 cells transiently using the dextran sulfate method described by Somparyrac et al., Proc. Natl. Acad. Sci.. 2:7575 (1981). 293 cells are grown to maximal density in a spinner flask and 700 μg pRK5-Bolekine DNA is added. The cells are first concentrated from the spinner flask by centrifugation and washed with PBS. The DNA-dextran precipitate is incubated on the cell pellet for four hours. The cells are treated with 20% glycerol for 90 seconds, washed with tissue culture medium, and re-introduced into the spinner flask containing tissue culture medium, 5 μg/ml bovine insulin and 0.1 μg/ml bovine transferrin. After about four days, the conditioned media is centrifuged and filtered to remove cells and debris. The sample containing expressed Bolekine polypeptide can then be concentrated and purified by any selected method, such as dialysis and/or column chromatography. In another embodiment, Bolekine polypeptide can be expressed in CHO cells. The pRK5-Bolekine vector can be transfected into CHO cells using known reagents such as CaP04 or DEAE-dextran. As described above, the cell cultures can be incubated, and the medium replaced with culture medium (alone) or medium containing a radiolabel such as 35s-memionine. After deterrnining the presence of Bolekine polypeptide, the culture medium may be replaced with serum free medium. Preferably, the cultures are incubated for about 6 days, and then the conditioned medium is harvested. The medium containing the expressed Bolekine polypeptide can then be concentrated and purified by any selected method. Epitope-tagged Bolekine polypeptide may also be expressed in host CHO cells. The Bolekine-encoding DNA may be subcloned out of the pRK5 vector. The subclone insert can undergo PCR to fuse in frame with a selected epitope tag such as a poly-his tag into a Baculovirus expression vector. The poly-his tagged Bolekine- encoding DNA insert can then be subcloned into a SV40 driven vector containing a selection marker such as DHFR for selection of stable clones. Finally, the CHO cells can be transfected (as described above) with the SV40 driven vector. Labeling may be performed, as described above, to verify expression. The culture medium containing the expressed poly-His tagged Bolekine polypeptide can then be concentrated and purified by any selected method, such as by Ni^-chelate affinity chromatography. EXAMPLE 5: Expression of a Bolekine Polypeptide in Yeast The following method describes recombinant expression of Bolekine polypeptides in yeast. First, yeast expression vectors are constructed for intracellular production or secretion of Bolekine polypeptide from the ADH2/GAPDH promoter. DNA encoding the Bolekine polypeptide of interest, a selected signal peptide and the promoter is inserted into suitable restriction enzyme sites in the selected plasmid to direct intracellular expression of the Bolekine polypeptide. For secretion, DNA encoding the Bolekine polypeptide can be cloned into the selected plasmid, together with DNA encoding the ADH2/GAPDH promoter, the yeast alpha-factor secretory signal/leader sequence, and linker sequences (if needed) for expression of the Bolekine polypeptide. Yeast cells, such as yeast strain AB110, can then be transformed with the expression plasmids described above and cultured in selected fermentation media. The transformed yeast supernatants can be analyzed by precipitation with 10% trichloroacetic acid and separation by SDS-PAGE, followed by staining of the gels with Coomassie Blue stain. Recombinant Bolekine polypeptide can subsequently be isolated and purified by removing the yeast cells from the fermentation medium by centrifugation and then concentrating the medium using selected cartridge filters. The concentrate containing the Bolekine polypeptide may further be purified using selected column chromatography resins. EXAMPLE 6: Preparation of Antibodies that Bind Bolekine Polypeptides This example illustrates the preparation of monoclonal antibodies which can specifically bind to Bolekine polypeptides. Techniques for producing the monoclonal antibodies are known in the art and are described, for instance, in Goding, supra. Immunogens that may be employed include purified Bolekine polypeptide, fusion proteins containing a Bolekine polypeptide, and cells expressing recombinant Bolekine polypeptide on the cell surface. Selection of the immunogen can be made by the skilled artisan without undue experimentation. Mice, such as Balb/c, are immunized with the Bolekine immunogen emulsified in complete Freund's adjuvant and injected subcutaneously or intraperitoneally in an amount from 1-100 micrograms. Alternatively, the immunogen is emulsified in MPL-TDM adjuvant (Ribi Immunochemical Research, Hamilton, MT) and injected into the animal's hind foot pads. The immunized mice are then boosted 10 to 12 days later with additional immunogen emulsified in the selected adjuvant. Thereafter, for several weeks, the mice may also be boosted with additional immunization injections. Serum samples may be periodically obtained from the mice by retro-orbital bleeding for testing in ELISA assays to detect anti-Bolekine polypeptide antibodies. After a suitable antibody titer has been detected, the animals "positive" for antibodies can be injected with a final intravenous injection of Bolekine polypeptide. Three to four days later, the mice are sacrificed and the spleen cells are harvested. The spleen cells are then fused (using 35% polyethylene glycol) to a selected murine myeloma cell line such as P3X63AgU.l, available from ATCC, No. CRL 1597. The fusions generate hybridoma cells which can then be plated in 96 well tissue culture plates containing HAT (hypoxanthine, aminopterin, and thymidine) medium to inhibit proliferation of non-fused cells, myeloma hybrids, and spleen cell hybrids. The hybridoma cells will be screened in an ELISA for reactivity against Bolekine polypeptide. Determination of "positive" hybridoma cells secreting the desired monoclonal antibodies against a Bolekine polypeptide is within the skill in the art. The positive hybridoma cells can be injected intraperitoneally into syngeneic Balb/c mice to produce ascites containing the anti-Bolekine polypeptide monoclonal antibodies. Alternatively, the hybridoma cells can be grown in tissue culture flasks or roller bottles. Purification of the monoclonal antibodies produced in the ascites can be accomplished using ammonium sulfate precipitation, followed by gel exclusion chromatography. Alternatively, affinity chromatography based upon binding of antibody to protein A or protein G can be employed. EXAMPLE 7: Expression of Bolekine Polypeptides in Baculovirus Infected Cells The following method describes recombinant expression of Bolekine polypeptides in baculovirus infected insect cells. In general, the Bolekine-encoding DNA is fused upstream of an epitope tag contained within a baculovirus expression vector. Such epitope tags include poly-his tags and immunoglobulin tags (like Fc regions of IgG). A variety of plasmids may be employed, including plasmids derived from commercially available plasmids such as ρVL1393 (Novagen). Briefly, the Bolekine-encoding DNA or the desired portion of the Bolekine-encoding DNA (such as the sequence encoding the extracellular domain of a transmembrane protein) is amplified by PCR with primers complementary to the 5' and 3' regions. The 5' primer may incorporate flanking (selected) restriction enzyme sites. The product is then digested with those selected restriction enzymes and subcloned into the expression vector. The fragment was then subcloned into the pb.PH.IgG vector via those respective sites. The pb.PH.IgG plasmid is a derivatives of the pVL1393 plasmid (Pharmingen) and encodes the Fc region of the human IgG gene downstream of the cloning site. In general, recombinant baculovirus is generated by co-transfecting the above plasmid and BaculoGold™ virus DNA (Pharmingen) into Spodoptera frugiperda ("Sf9") cells (ATCC CRL 1711) using lipofectin (commercially available from GIBCO-BRL). After 4 to 5 days of incubation at 28°C, the released viruses are harvested and used for further amplifications. Viral infection and protein expression is performed as described by O'Reilley et al., Baculovirus expression vectors: A laboratory Manual, Oxford: Oxford University Press (1994). In this case, The pb.PH.SST DNA.IgG plasmid was co-transfected with Baculogold Baculovirus DNA (Pharmingen) using Lipofectin (Gibco BRL) into 10 5 Sf9 cells grown in Hink's TNM-FH medium (JRH Biosciences) supplemented with 10% fetal bovine serum (FBS) (Hyclone). Cells were incubated for 5 days at 28 °C. The supernatant was harvested and subsequently used for the 1st viral amplification by infecting Sf9 cells in Hink's TNM-FH medium supplemented with 10% FBS at an approximate multiplicity of infection (MOI) of 10. Cells were incubated for 3 days at 28 °C. The supernatant was harvested and the expression of the recombinant Bolekin-IgG was determined by batching binding of 1 mL of supernatant to 30 μL of Protein-A Sepharose CL-4B beads (Pharmacia) followed by subsequent SDS-PAGE analysis comparing to a known concentration of protein standard marker by Coomassie blue staining. The first viral amplification supernatant was used to infect a 500 mL spinner culture of Sf9 cells grown in ESF-921 medium (Expression Systems LLC) at an approximate MOI of 0.1. Cells were incubated for 3 days at 28°C. The supernatant was harvested and filtered. Batching binding and SDS-PAGE analysis were repeated to confirm expression in the spinner culture. The 500 mL of supernatant was subsequently submitted for purification. In general, expressed poly-his tagged Bolekine polypeptide can then be purified, for example, by Ni^ + - chelate affinity chromatography as follows. Extracts are prepared from recombinant virus-infected Sf9 cells as described by Rupert et al. , Nature, 362: 175-179 (1993). Briefly, Sf9 cells are washed, resuspended in sonication buffer (25 mL Hepes, pH 7.9; 12.5 mM MgCl 2 ; 0.1 mM EDTA; 10% Glycerol; 0.1 % NP-40; 0.4 M KC1), and sonicated twice for 20 seconds on ice. The sonicates are cleared by centrifugation, and the supernatant is diluted 50-fold in loading buffer (50 mM phosphate, 300 mM NaCl, 10 % Glycerol, pH 7.8) and filtered through a 0.45 micron filter. A Ni^ + -NTA agarose column (commercially available from Qiagen) is prepared with a bed volume of 5 mL, washed with 25 mL of water and equilibrated with 25 mL of loading buffer. The filtered cell extract is loaded onto the column at 0.5 mL per minute. The column is washed to baseline A280 with loading buffer, at which point fraction collection is started. Next, the column is washed with a secondary wash buffer (50 mM phosphate; 300 mM NaCl, 10% Glycerol, pH 6.0), which elutes nonspecifically bound protein. After reaching A28O baseline again, the column is developed with a 0 to 500 mM Imidazole gradient in the secondary wash buffer. One mL fractions are collected and analyzed by SDS-PAGE and silver staining or western blot with N + -NTA-conjugated to alkaline phosphatase (Qiagen). Fractions containing the eluted Hisi Q -tagged Bolekine polypeptide are pooled and dialyzed against loading buffer. Alternatively, purification of the IgG tagged (or Fc tagged) Bolekine polypeptide can be performed using known chromatography techniques, including for instance, Protein A or protein G column chromatography. In this case, the conditioned media from the transfected Sf9 cells (500 mL, see above) were harvested by centrifugation to remove the cells and filtered through 0.22 micron filters. Immunoadhesin (Fc containing) constructs of Bolekine protein were purified from the conditioned media. The conditioned media was pumped onto a 5 ml Protein A column (Pharmacia) which had been equilibrated in 20 mM Na phosphate, pH 6.8, buffer. After loading, the column was washed extensively with equilibration buffer before elusion with 100 mM citric acid, pH 3.5. The eluted protein was immediately neutralized by collecting 1 ml fractions into tubes containing 275 μL of 1 M Tris, pH 9, buffer. The highly purified protein was subsequently desalted into a storage buffer containing 10 mM Hepes, 0.14 M NaCl and 4% mannitol, pH 6.8, with a 25 ml G25 Superfine (Pharmacia) column and stored at -80° C. The homogeneity of the protein was assessed by SDS polyacrylamide gels and by N-terminal amino acid sequencing by Edman degradation. Purified protein encoded by Bolekine was separated on a tris-HCl gel and electroblotted to a PVDF membrane. The band of interest was excised and then subjected to Edman degradation in order to confirm the protein product. EXAMPLE 8: Northern Blot Analysis Expression of Bolekine mRNA in human tissues was examined by Northern blot analysis. In general, human RNA blots were hybridized to a ^^p-labelled DΝA probe based on the full length Bolekine cDΝA; the probe was generated by digesting and purifying the Bolekine cDΝA insert. Human fetal RΝA blot MTΝ (Clontech) and human adult RΝA blot MTΝ-H (Clontech) were incubated with the DΝA probes. Blots were incubated with the probes in hybridization buffer (5 X SSPE; 2 X Denhardt's solution; 100 mg/mL denatured sheared salmon sperm DΝA; 50% formamide; 2% SDS) for 60 hours at 42°C. The blots were washed several times in 2 X SSC; 0.05% SDS for 1 hour at room temperature, followed by a 30 minute wash in 0.1X SSC; 0.1% SDS at 50°C. The blots were developed after overnight exposure by phosphorimager analysis (Fuji). In this case, Northern blots containing human poly (A) +RNA from various tissues (2 g/lane) were purchased from Clontech. A 469-bp fragment containing the entire coding region of Bolekine was amplified by PCR using the following two primers, forward and reverse, respectively: Forward Primer: 5'AGCGCACGGCCACAGACAG 3'(SEQ ID NO:6) and Reverse Primer: 5'GACCCTGCGCTTCTCGTTCCA 3' (SEQ ID NO:7). A Bolekine-specific p2p]dCTP-labeled cDNA probe was synthesized by random priming of this 469-bp fragment (High Prime, Boehringer Mannheim) and unincorporated nucleotides were removed (NucTrap Probe Purification Column, Stratagene). Membranes were analyzed by Northern blot hybridization as previously described (McMaster, M.T. et al., J. Immunol. 154(8):3771-3778, 1995). As shown in Figure 3, Bolekine mRNA transcripts were detected. A 2 kb transcript was detected at low levels in various tissues, with moderate levels of expression in spleen, lymph node, and colon, and highest levels in kidney and small intestine. No expression can be detected in lung and unstimulated peripheral blood leukocytes (PBL). EXAMPLE 9: In Situ Hybridization Showing Expression Patterns Formalin-fixed, paraffin-embedded normal and diseased human fetal and adult tissues were sectioned, deparaffinized, deproteinated in proteinase K (20 mg/ml) for 15 minutes at 37 °C, and further processed for in situ hybridization as described (Lu, L.H., and N.A. Gillett, Cell Vision, 1:169-176, 1994). A [ 33 -P] UTP- labeled antisense riboprobe was generated from a 463 bp PCR product (primer sequences as described for Northern analysis) and hybridized at 55 °C overnight. The slides were dipped in Kodak NTB2 nuclear track emulsion and exposed for 4 weeks. Fetal tissues examined include: placenta, umbilical cord, liver, kidney, adrenals, thyroid, lungs, heart, great vessels, esophagus, stomach, small intestine, spleen, thymus, pancreas, brain, eye, spinal cord, body wall, pelvis and lower limb. Adult tissues examined include liver, kidney, adrenal myocardium, aorta, spleen, lymph node, pancreas, lung, skin, cerebral cortex (rm), hippocampus (rm), eye, stomach, gastric carcinoma, colon, colonic carcinoma, thyroid (chimp), parathyroid (chimp), ovary (chimp) and chondrosarcoma. Acetaminophen induced liver injury and hepatic cirrhosis. Results are shown in Figures 4A-4E which are photomicrographs, including both dark field (right frame) and H&E stained tissue in bright field (left frame). An intense signal was visible in various human tissues. Figure 4A depicts normal skin which had specific strong expression in the epithelial cells of the stratum basale; this deepest most layer of the epidermis is the single cell thick layer of cells along the basement membrane which are the progenitors for all of the overlying epidermal cells in the skin. There was no expression in epidermal cells in the overlying layers (stratum spinosum, stratum granulosum etc.). Expression was also apparent in the dermis, which is the connective tissue immediately underlying the epidermis. Figure 4B depicts fetal kidney. In the fetal kidney, expression was specific in developing tubules and expression was seen in the tubular epithelium. Figure 4C and Figure 4D are fetal gut and adult gut respectively. Sections of normal adult human large bowel and fetal bowel were evaluated for expression. Both bowel specimens had specific moderate to strong expression in a multifocal pattern within the lamina propria of villi. Figure 4E are sections of cerebrum that were evaluated for expression. Sections of cerebrum had strong specific expression in a subset of superfical cortical neurons; the pattern was distinct and suggests delineation of a specific population of neurons present in the cortex. EXAMPLE 10: Stimulatory Activity in Mixed Lymphocyte Reaction (MLR) Assay (no.24) This example shows that the polypeptides of the invention are active as stimulators of the proliferation of T-lymphocytes. Compounds which stimulate proliferation of lymphocytes are useful therapeutically where enhancement of an immune response is beneficial. A therapeutic agent may also take the form of antagonists of Bolekine, for example, murine-human ehimeric, humanized or human antibodies against the polypeptide, which would be expected to inhibit T-lymphocyte proliferation. The basic protocol for this assay is described in Current Protocols in Immunology, unit 3.12; edited by J. E. Coligan, A. M. Kruisbeek, D. H. Marglies, E. M. Shevach, W. Strober, National Institutes of Health, Published by John Wiley & Sons, Inc. More specifically, in one assay variant, peripheral blood mononuclear cells (PBMC) are isolated from mammalian individuals, for example a human volunteer, by leukopheresis (one donor will supply stimulator PBMCs, the other donor will supply responder PBMCs). If desired, the cells are frozen in fetal bovine serum and DMSO after isolation. Frozen cells may be thawed overnight in assay media (37 °C, 5% C02 ) and then washed and resuspended to 3 x IO 6 cells/ml of assay media (RPMI; 10% fetal bovine serum, 1% penicillin/streptomycin, 1% glutamine, 1 % HEPES, 1% non-essential amino acids, 1% pyruvate). The stimulator PBMCs are prepared by irradiating the cells (about 3000 Rads). The assay is prepared by plating in triplicate wells a mixture of: 100:1 of test sample diluted to 1 % or to 0.1 % ; 50:1 of irradiated stimulator cells and 50:1 of responder PBMC cells. 100 microliters of cell culture media or 100 microliter of CD4-IgG is used as the control. The wells are then incubated at 37°C, 5 % C02 for 4 days. On day 5 and each well is pulsed with tritiated thymidine (1.0 mCi/well; Amersham). After 6 hours the cells are washed 3 times and then the uptake of the label is evaluated. In another variant of this assay, PBMCs are isolated from the spleens of Balb/c mice and C57B6 mice. The cells are teased from freshly harvested spleens in assay media (RPMI; 10% fetal bovine serum, 1 % penicillin/streptomycin, 1% glutamine, 1% HEPES, 1 % non-essential amino acids, 1% pyruvate) and the PBMCs are isolated by overlaying these cells over Lympholyte M (Organon Teknika), centrifuging at 2000 rpm for 20 minutes, collecting and washing the mononuclear cell layer in assay media and resuspending the cells to lx 107 cells/ml of assay media. The assay is then conducted as described above. The results of this assay for compounds of the invention are shown below in Table 7. Positive increases over control are considered positive with increases of greater than or equal to 180% being preferred. However, any value greater than control indicates a stimulatory effect for the test protein. TABLE 7 PRO PRO Concentration Percent Increase Over Control Bolekine 12.40 nM 112.0 Bolekine 124.00 nM 192.7 EXAMPLE 11: Skin Vascular Permeability Assay (no.64) This assay shows that Bolekine stimulates an immune response and can induce inflammation by inducing mononuclear cell, eosinophil and PMN infiltration at the site of injection of the animal. This skin vascular permeability assay is conducted as follows. Hairless guinea pigs weighing 350 grams or more are anesthetized with ketamine (75-80 mg/Kg) and 5 mg/Kg Xylazine intramuscularly (IM). A sample of purified Bolekine polypeptide or a conditioned media test sample is injected intradermally onto the backs of the test animals with 100 mL per injection site. It is possible to have about 10-30, preferably about 16-24, injection sites per animal. One mL of Evans blue dye (1% in physiologic buffered saline) is injected intracardially. Blemishes at the injection sites are then measured (mm diameter) at lhr, 6 hrs and 24 hrs post injection. Animals were sacrificed at the appropriate time after injection. Each skin injection site is biopsied and fixed in paraformaldehyde. The skins are then prepared for histopathalogic evaluation. Each site is evaluated for inflammatory cell infiltration into the skin. Sites with visible inflammatory cell inflammation are scored as positive. Inflammatory cells may be neutrophilic, eosinophilic, monocytic or lymphocytic At least a minimal perivascular infiltrate at the injection site is scored as positive, no infiltrate at the site of injection is scored as negative. Bolekine scored positive in this assay EXAMPLE 12: Neuronal differentiation of ES cells. (No. 137) ES cells are grown at clonal density on 24-well plates in ES + LIF medium [to stop differentiation] for two days to establish small colonies. The medium is then changed to KSR medium, LIF containing various amounts of Bolekine protein and the ES clones are allowed to grow and differentiate for 7 days in culture. On the 7th day the cells are fixed and processed for immunocytochemistry with antibodies raised against the neuronal marker MAP2. The degree of neuronal differentiation is assessed using fluorescence microscopy. ES media-High glucose DMEM- 10 % Fetal Calf Serum- SC media supplement-plus LJJF- KSR medium-GMEM- 10% KSR [Knock out serum replacement supplement]- glutamine- Pen/Strep- non-essential amino acids- and 2- ME. Fixation-4% paraformaldehyde- MAP2 antibody [Pharmingen] diluted 1:1000 inPBST [0.1% Triton] with 3% normal goat serum. Results will be calculated as the % of ES colonies containing neurons and the % of neurons within individual colonies. Wells that have neuronal colony and cell counts lOx above background will be considered positive, containing a protein that influences neuronal differentiation. Bolekine at a final concentration of 124.00 nM tested positive for neuronal differentiation. EXAMPLE 13: Purification of Bolekine Polypeptides Using Specific Antibodies Native or recombinant Bolekine polypeptides may be purified by a variety of standard techniques in the art of protein purification. For example, pro-Bolekine polypeptide, mature Bolekine polypeptide, or pre- Bolekine polypeptide is purified by immunoaffinity chromatography using antibodies specific for the Bolekine polypeptide of interest. In general, an immunoaffinity column is constructed by covalently coupling the anti-Bolekine polypeptide antibody to an activated chromatographic resin. Polyclonal immunoglobulins are prepared from immune sera either by precipitation with ammonium sulfate or by purification on immobilized Protein A (Pharmacia LKB Biotechnology, Piscataway, N.J.). Likewise, monoclonal antibodies are prepared from mouse ascites fluid by ammonium sulfate precipitation or chromatography on immobilized Protein A. Partially purified immunoglobulin is covalently attached to a chromatographic resin such as CnBr-activated SEPHAROSE™ (Pharmacia LKB Biotechnology). The antibody is coupled to the resin, the resin is blocked, and the derivative resin is washed according to the manufacturer's instructions. Such an immunoaffinity column is utilized in the purification of Bolekine polypeptide by preparing a fraction from cells containing Bolekine polypeptide in a soluble form. This preparation is derived by solubilization of the whole cell or of a subcellular fraction obtained via differential centrifugation by the addition of detergent or by other methods well known in the art. Alternatively, soluble Bolekine polypeptide containing a signal sequence may be secreted in useful quantity into the medium in which the cells are grown. A soluble Bolekine polypeptide-containing preparation is passed over the immunoaffinity column, and the column is washed under conditions that allow the preferential absorbance of Bolekine polypeptide (e.g. , high ionic strength buffers in the presence of detergent). Then, the column is eluted under conditions that disrupt antibody/Bolekine polypeptide binding (e.g., a low pH buffer such as approximately pH 2-3, or a high concentration of a chaotrope such as urea or thiocyanate ion), and Bolekine polypeptide is collected. EXAMPLE 14: Drug Screening This invention is particularly useful for screening compounds by using Bolekine polypeptides or binding fragment thereof in any of a variety of drug screening techniques. The Bolekine polypeptide or fragment employed in such a test may either be free in solution, affixed to a solid support, borne on a cell surface, or located intracellularly. One method of drug screening utilizes eukaryotic or prokaryotic host cells which are stably transformed with recombinant nucleic acids expressing the Bolekine polypeptide or fragment. Drugs are screened against such transformed cells in competitive binding assays . Such cells , either in viable or fixed form, can be used for standard binding assays. One may measure, for example, the formation of complexes between Bolekine polypeptide or a fragment and the agent being tested. Alternatively, one can examine the diminution in complex formation between the Bolekine polypeptide and its target cell or target receptors caused by the agent being tested. Thus, the present invention provides methods of screening for drugs or any other agents which can affect a Bolekine polypeptide-associated disease or disorder. These methods comprise contacting such an agent with an Bolekine polypeptide or fragment thereof and assaying (i) for the presence of a complex between the agent and the Bolekine polypeptide or fragment, or (ii) for the presence of a complex between the Bolekine polypeptide or fragment and the cell, by methods well known in the art. In such competitive binding assays, the Bolekine polypeptide or fragment is typically labeled. After suitable incubation, free Bolekine polypeptide or fragment is separated from that present in bound form, and the amount of free or uncomplexed label is a measure of the ability of the particular agent to bind to Bolekine polypeptide or to interfere with the Bolekine polypeptide/cell complex. Another technique for drug screening provides high throughput screening for compounds having suitable binding affinity to a polypeptide and is described in detail in WO 84/03564, published on September 13, 1984. Briefly stated, large numbers of different small peptide test compounds are synthesized on a solid substrate, such as plastic pins or some other surface. As applied to a Bolekine polypeptide, the peptide test compounds are reacted with Bolekine polypeptide and washed. Bound Bolekine polypeptide is detected by methods well known in the art. Purified Bolekine polypeptide can also be coated directly onto plates for use in the aforementioned drug screening techniques. In addition, non-neutralizing antibodies can be used to capture the peptide and immobilize it on the solid support. This invention also contemplates the use of competitive drug screening assays in which neutralizing antibodies capable of binding Bolekine polypeptide specifically compete with a test compound for binding to Bolekine polypeptide or fragments thereof. In this manner, the antibodies can be used to detect the presence of any peptide which shares one or more antigenic determinants with Bolekine polypeptide. EXAMPLE 15: Rational Drug Design The goal of rational drug design is to produce structural analogs of biologically active polypeptide of interest (i.e., a Bolekine polypeptide) or of small molecules with which they interact, e.g. , agonists , antagonists , or inhibitors. Any of these examples can be used to fashion drugs which are more active or stable forms of the Bolekine polypeptide or which enhance or interfere with the function of the Bolekine polypeptide in vivo (cf., Hodgson, Bio/Technology. 9: 19-21 (1991)). In one approach, the three-dimensional structure of the Bolekine polypeptide, or of a Bolekine polypeptide-inhibitor complex, is determined by x-ray crystallography, by computer modeling or, most typically, by a combination of the two approaches. Both the shape and charges of the Bolekine polypeptide must be ascertained to elucidate the structure and to determine active site(s) of the molecule. Less often, useful information regarding the structure of the Bolekine polypeptide may be gained by modeling based on the structure of homologous proteins. In both cases, relevant structural information is used to design analogous Bolekine polypeptide-like molecules or to identify efficient inhibitors. Useful examples of rational drug design may include molecules which have improved activity or stability as shown by Braxton and Wells, Biochemistry. 31:7796-7801 (1992) or which act as inhibitors, agonists, or antagonists of native peptides as shown by Athauda et al, J. Biochem.. 113:742-746 (1993). It is also possible to isolate a target-specific antibody, selected by functional assay, as described above, and then to solve its crystal structure. This approach, in principle, yields a pharmacore upon which subsequent drug design can be based. It is possible to bypass protein crystallography altogether by generating anti-idiotypic antibodies (anti-ids) to a functional, pharmacologically active antibody. As a mirror image of a mirror image, the binding site of the anti-ids would be expected to be an analog of the original receptor. The anti-id could then be used to identify and isolate peptides from banks of chemically or biologically produced peptides . The isolated peptides would then act as the pharmacore. By virtue of the present invention, sufficient amounts of the Bolekine polypeptide may be made available to perform such analytical studies as X-ray crystallography. In addition, knowledge of the Bolekine polypeptide amino acid sequence provided herein will provide guidance to those employing computer modeling techniques in place of or in addition to x-ray crystallography. Deposit of Material The following materials have been deposited with the American Type Culture Collection, 10801 University Blvd., Manassas, VA 20110-2209, USA (ATCC): Material ATCC Pep. No. Deposit Date DNA39523- 1192 (Bolekine) 209424 October 31 , 1997 These deposits were made under the provisions of the Budapest Treaty on the International Recognition of the Deposit of Microorganisms for the Purpose of Patent Procedure and the Regulations thereunder (Budapest Treaty). This assures maintenance of a viable culture of the deposit for 30 years from the date of deposit. The deposits will be made available by ATCC under the terms of the Budapest Treaty, and subject to an agreement between Genentech, Inc. and ATCC, which assures permanent and unrestricted availability of the progeny of the culture of the deposit to the public upon issuance of the pertinent U.S. patent or upon laying open to the public of any U.S. or foreign patent application, whichever comes first, and assures availability of the progeny to one determined by the U.S. Commissioner of Patents and Trademarks to be entitled thereto according to 35 USC § 122 and the Commissioner's rules pursuant thereto (including 37 CFR § 1.14 with particular reference to 886 OG 638). The assignee of the present application has agreed that if a culture of the materials on deposit should die or be lost or destroyed when cultivated under suitable conditions, the materials will be promptly replaced on notification with another of the same. Availability of the deposited material is not to be construed as a license to practice the invention in contravention of the rights granted under the authority of any government in accordance with its patent laws. The foregoing written specification is considered to be sufficient to enable one skilled in the art to practice the invention. The present invention is not to be limited in scope by the construct deposited, since the deposited embodiment is intended as a single illustration of certain aspects of the invention and any constructs that are functionally equivalent are within the scope of this invention. The deposit of material herein does not constitute an admission that the written description herein contained is inadequate to enable the practice of any aspect of the invention, including the best mode thereof, nor is it to be construed as limiting the scope of the claims to the specific illustrations that it represents. Indeed, various modifications of the invention in addition to those shown and described herein will become apparent to those skilled in the art from the foregoing description and fall within the scope of the appended claims.

Claims: WHAT IS CLAIMED IS: 1. An isolated nucleic acid molecule which comprises (a) a DNA molecule encoding a Bolekine polypeptide comprising the sequence of amino acid residues from about 1 or about 34 to about 111 of Figure 2 (SEQ ID NO:2), or (b) the complement of the DNA molecule of Bolekine (a). 2. The isolated nucleic acid molecule of Claim 1 comprising the sequence of nucleotide positions from about 167 or about 269 to about 499 of Figure 1 (SEQ ID NO:l). 3. The isolated nucleic acid molecule of Claim 1 comprising the nucleotide sequence of Figure 1 (SEQ ID NO: 1). 4. The isolated nucleic acid molecule of Claim 1 comprising the full-length polypeptide coding sequence of the human protein cDNA deposited with the ATCC on October 31, 1997 under ATCC Deposit No. 209424 (DNA39523-1192). 5. An isolated nucleic acid molecule comprising DNA which comprises (a) a DNA molecule encoding the same mature polypeptide encoded by the human protein cDNA deposited with the ATCC on October 31, 1997 under ATCC Deposit No. 209424 (DNA39523-1192), or (b) the complement of the DNA molecule of (a). 6. A nucleic acid molecule deposited with the ATCC under accession number 209424 (DNA39523-1192). 7. An isolated nucleic acid molecule encoding a Bolekine polypeptide comprising DNA that hybridizes to the complement of the nucleic acid sequence that encodes amino acids 1 or about 34 to about 111 of Figure 2 (SEQ ID NO:2). 8. The isolated nucleic acid molecule of Claim 7, wherein the nucleic acid that encodes amino acids 1 or about 34 to about 111 of Figure 2 (SEQ ID NO:2) comprises nucleotides 167 or about 269 to about 499 of Figure 1 (SEQ ID NO: 1). 9. The isolated nucleic acid molecule of Claim 7 , wherein the hybridization occurs under stringent hybridization and wash conditions. 10. A vector comprising the nucleic acid molecule of Claim 1 . 11. The vector of Claim 10, wherein said nucleic acid molecule is operably linked to control sequences recognized by a host cell transformed with the vector. 12. A host cell comprising the vector of Claim 10. 13. The host cell of Claim 12, wherein said cell is a CHO cell, an E. coli. bacterium, or a yeast cell. 14. A process for producing a Bolekine polypeptide comprising culturing the host cell of Claim 12 under conditions suitable for expression of said Bolekine polypeptide and recovering said Bolekine polypeptide from the cell culture. 15. The isolated Bolekine polypeptide comprising amino acid residues 1 or about 34 to about 111 of Figure 2 (SEQ ID NO:2). 16. The isolated Bolekine polypeptide which is encoded by the cDNA insert of the vector deposited with the ATCC on October 31, 1997 as ATCC Deposit No. 209424 (DNA39523-1192). 17. An isolated Bolekine polypeptide comprising the sequence of amino acid residues from 1 or about 34 to about 111 of Figure 2 (SEQ ID NO: 2), or a fragment thereof sufficient to provide a binding site for an anti-Bolekine antibody. 18. An isolated polypeptide produced by (i) hybridizing a test DNA molecule under stringent conditions with (a) a DNA molecule encoding a Bolekine polypeptide comprising the sequence of amino acid residues from 1 or about 34 to about 111 of Figure 2 (SEQ ID NO:2), or (b) the complement of the DNA molecule of (a), (ii) culturing a host cell comprising said test DNA molecule under conditions suitable for the expression of said polypeptide, and (iii) recovering said polypeptide from the cell culture. 19. A ehimeric molecule comprising a Bolekine polypeptide fused to a heterologous amino acid sequence. 20. The ehimeric molecule of Claim 19, wherein said heterologous amino acid sequence is an epitope tag sequence. 21. The ehimeric molecule of Claim 19, wherein said heterologous amino acid sequence is a Fc region of an immunoglobulin. 22. An antibody which specifically binds to a Bolekine polypeptide. 23. The antibody of Claim 22, wherein said antibody is a monoclonal antibody. 24. The antibody of Claim 22 wherein said antibody is a humanized antibody or an antibody fragment. 25. An agonist to a Bolekine polypeptide. 26. An antagonist to a Bolekine polypeptide. 27. A composition of matter comprising (a) a Bolekine polypeptide, (b) an agonist to a Bolekine polypeptide, (c) an antagonist to a Bolekine polypeptide, or (d) an anti-Bolekine antibody, in admixture with a pharmaceutically acceptable carrier. 28. The composition of matter of Claim 27, which is useful for the treatment of an immune related disease in a mammal. 29. The composition of matter of Claim 27, wherein (a), (b), (c) or (d) is capable of (i) enhancing the proliferation of T-lymphocytes in a mammal, or (ii) increasing infiltration of inflammatory cells into a tissue of a mammal. 30. The composition of matter of Claim 27 comprising a therapeutically effective amount of (a), (b), (c) or (d). 31. An article of manufacture, comprising: a container; a label on said container; and a composition of matter comprising (a) a polypeptide of Claim 17, (b) an agonist of said polypeptide, (c) an antagonist of said polypeptide, or (d) an antibody that binds to said polypeptide, contained within said container, wherein label on said container indicates that said composition of matter can be used for treating an immune related disease. 32. A method of treating an immune related disorder in a mammal in need thereof comprising aclministering to said mammal a therapeutically effective amount of (a) a polypeptide of Claim 17, (b) an agonist of said polypeptide, (c) an antagonist of said polypeptide, or (d) an antibody that binds to said polypeptide. 33. The method of Claim 32, wherein the immune related disorder is systemic lupus erythematosis, rheumatoid arthritis, osteoarthritis, juvenile chronic arthritis, a spondyloarthropathy, systemic sclerosis, an idiopathic inflammatory myopathy, Sjδgren's syndrome, systemic vasculitis, sarcoidosis, autoimmune hemolytic anemia, autoimmune thrombocytopenia, thyroiditis, diabetes mellitus, immune-mediated renal disease, a demyelinating disease of the central or peripheral nervous system, idiopathic demyelinating polyneuropathy, Guillain-Barre syndrome, a chronic inflammatory demyelinating polyneuropathy, a hepatobiliary disease, infectious or autoimmune chronic active hepatitis, primary biliary cirrhosis, granulomatous hepatitis, sclerosing cholangitis, inflammatory bowel disease, gluten-sensitive enteropathy, Whipple's disease, an autoimmune or immune-mediated skin disease, a bullous skin disease, erythema multiforme, contact dermatitis, psoriasis, an allergic disease, asthma, allergic rhinitis, atopic dermatitis, food hypersensitivity, urticaria, an immunologic disease of the lung, eosinophilic pneumonias, idiopathic pulmonary fibrosis, hypersensitivity pneumonitis, a transplantation associated disease, graft rejection or graft-versus-host-disease. 34. A method for determining the presence of a Bolekine polypeptide in a sample suspected of containing said polypeptide, said method comprising exposing said sample to an anti-Bolekine antibody and deterinining binding of said antibody to a component of said sample. 35. A method of diagnosing an immune related disease in a mammal, said method comprising detecting the level of expression of a gene encoding Bolekine polypeptide (a) in a test sample of tissue cells obtained from the mammal, and (b) in a control sample of known normal tissue cells of the same cell type, wherein a higher or lower level of expression of said gene in the test sample as compared to the control sample is indicative of the presence of an immune related disease in the mammal from which the test tissue cells were obtained. 36. A method of diagnosing an immune related disease in a mammal, said method comprising (a) contacting an an anti-Bolekine antibody with a test sample of tissue cells obtained from said mammal and (b) detecting the formation of a complex between the antibody and the polypeptide in the test sample, wherein formation of said complex is indicative of the presence of an immune related disease in the mammal from which the test tissue cells were obtained. 37. A method of identifying a compound that inhibits the activity of a Bolekine polypeptide, said method comprising contacting cells which normally respond to said polypeptide with (a) said polypeptide and (b) a candidate compound, and deteπnining the lack responsiveness by said cell to (a). 38. A method of identifying a compound that inhibits the expression of a gene encoding a Bolekine polypeptide, said method comprising contacting cells which normally express said polypeptide with a candidate compound, and deteπruning the lack of expression said gene. 39. The method of Claim 38, wherein said candidate compound is an antisense nucleic acid. 40. A method of identifying a compound that n imics the activity of a Bolekine polypeptide, said method comprising contacting cells which normally respond to said polypeptide with a candidate compound, and deterrnining the responsiveness by said cell to said candidate compound. 41. A method of stimulating the proliferation of T-lymphocytes , said method comprising contacting T-lymphocytes with an effective amount of (a) a Bolekine polypeptide or (b) an agonist of (a), wherein the proliferation of said T-lymphocytes is stimulated. 42. A method of inhibiting the proliferation of T-lymphocytes, said method comprising contacting T-lymphocytes with an effective amount of an antagonist of a Bolekine polypeptide, wherein the proliferation of said T-lymphocytes is inhibited. 43. A method of enhancing the infiltration of inflammatory cells into a tissue of a mammal, said method comprising administering to said tissue an effective amoimt of (a) Bolekine polypeptide or (b) an agonist of (a), wherein said infiltration is enhanced. 44. The method of Claim 43, wherein said inflammatory cells are mononuclear cells, eosinophils or polymorphonuclear neutrophils (PMNs). 45. A method of inducing the differentiation of puripotent cells into neuronal cells in a mammal, said method comprising aclministering an effective amount of (a) a Bolekine polypeptide or (b) an antagonist of Bolekine polypeptide, wherein said cells differentiate to a state wherein neuronal markers can be detected. 46. The method of Claim 45, wherein said neuronal marker is MAP2.

Inventors: FONG SHERMAN, GODDARD AUDREY, HILLAN KENNETH J, ROTH IRIS, WOOD WILLIAM I, FONG, SHERMAN, GODDARD, AUDREY, HILLAN, KENNETH, J., ROTH, IRIS, WOOD, WILLIAM, I.
Applicants: GENENTECH INC, GENENTECH, INC.
Application year: 2001
Main classification: C07K14
IPC codes: A61K38, A61K39, A61K45, A61P1, A61P3, A61P5, A61P7, A61P11, A61P13, A61P17, A61P19, A61P25, A61P29, A61P37, C07K14, C07K16, C07K19, C12N1, C12N5, C12N15, C12P21, C12Q1, G01N33