COMPOUNDS AND METHODS FOR IMMUNOTHERAPY AND DIAGNOSIS OF TUBERCULOSIS

Abstract: Compounds and methods for inducing protective immunity against tuberculosis are disclosed. The compounds provided include polypeptides that contain at least one immunogenic portion of one or more M. tuberculosis proteins and DNA molecules encoding such polypeptides. Such compounds may be formulated into vaccines and/or pharmaceutical compositions for immunization against M. tuberculosis infection, or may be used for the diagnosis of tuberculosis.

Description: J Description *« 5 COMPOUNDS AND METHODS FOR IMMUNOTHERAPY AND DIAGNOSIS OF TUBERCULOSIS Technical Field 10 The present invention relates generally to detecting, treating and preventing Mycobacterium tuberculosis infection. The invention is more particularly related to polypeptides comprising a Mycobacterium tuberculosis antigen, or a portion or other variant thereof, and the use of such polypeptides for diagnosing and vaccinating against Mycobacterium tuberculosis infection. 15 Background ofthe Invention Tuberculosis is a chronic, infectious disease, that is generally caused by infection with Mycobacterium tuberculosis. It is a major disease in developing countries, as well as an increasing problem in developed areas of the world, with about 20 8 million new cases and 3 million deaths each year. Although the infection may be asymptomatic for a considerable period of time, the disease is most commonly manifested as an acute inflammation ofthe lungs, resulting in fever and a nonproductive cough. If left untreated, serious complications and death typically result. Although tuberculosis can generally be controlled using extended 25 antibiotic therapy, such treatment is not sufficient to prevent the spread of the disease. Infected individuals may be asymptomatic, but contagious, for some time. In addition, although compliance with the treatment regimen is critical, patient behavior is difficult to monitor. Some patients do not complete the course of treatment, which can lead to ineffective treatment and the development of drug resistance. Inhibiting the spread of tuberculosis requires effective vaccination and accurate, early diagnosis ofthe disease. Currently, vaccination with live bacteria is the most efficient method for inducing protective immunity. The most common Mycobacterium employed for this purpose is Bacillus Calmette-Guerin (BCG), an avirulent strain of Mycobacterium bovis. However, the safety and efficacy of BCG is a source of controversy and some countries, such as the United States, do not vaccinate the general public. Diagnosis is commonly achieved using a skin test, which involves intradermal exposure to tuberculin PPD (protein-purified derivative). Antigen-specific T cell responses result in measurable induration at the injection site by 48-72 hours after injection, which indicates exposure to Mycobacterial antigens. Sensitivity and specificity have, however, been a problem with this test, and individuals vaccinated with BCG cannot be distinguished from infected individuals. While macrophages have been shown to act as the principal effectors of M tuberculosis immunity, T cells are the predominant inducers of such immunity. The essential role of T cells in protection against M. tuberculosis infection is illustrated by the frequent occurrence of M. tuberculosis in AIDS patients, due to the depletion of CD4 T cells associated with human immunodeficiency virus (HIV) infection. Mycobacterium-reactive CD4 T cells have been shown to be potent producers of gamma-interferon (IFN-γ), which, in turn, has been shown to trigger the anti- mycobacterial effects of macrophages in mice. While the role of IFN-γ in humans is less clear, studies have shown that 1,25-dihydroxy- vitamin D3, either alone or in combination with IFN-γ or tumor necrosis factor-alpha, activates human macrophages to inhibit M. tuberculosis infection. Furthermore, it is known that IFN-γ stimulates human macrophages to make 1,25-dihydroxy- vitamin D3. Similarly, IL-l 2 has been shown to play a role in stimulating resistance to M. tuberculosis infection. For a review of the immunology of M. tuberculosis infection see Chan and Kaufmann in Tuberculosis: Pathogenesis, Protection and Control, Bloom (ed.), ASM Press, Washington, DC, 1994. Accordingly, there is a need in the art for improved vaccines and methods for preventing, treating and detecting tuberculosis. The present invention fulfills these needs and further provides other related advantages. Summary ofthe Invention Briefly stated, this invention provides compounds and methods for preventing and diagnosing tuberculosis. In one aspect, polypeptides are provided comprising an immunogenic portion of a soluble M. tuberculosis antigen, or a variant of such an antigen that differs only in conservative substitutions and/or modifications. In one embodiment of this aspect, the soluble antigen has one of the following N-terminal sequences: (a) Asp-Pro-Val-Asp-Ala-Nal-Ile-Asn-Thr-Thr-Cys-Asn-Tyr-Gly- Gln-ValNal-Ala-Ala-Leu; (SEQ ID No. 120) (b) Ala-Val-Glu-Ser-Gly-Met-Leu-Ala-Leu-Gly-Thr-Pro-Ala-Pro- Ser; (SEQ ID No. 121) (c) Ala-Ala-Met-Lys-Pro-Arg-Thr-Gly-Asp-Gly-Pro-Leu-Glu-Ala- Ala-Lys-Glu-Gly-Arg; (SEQ ID No. 122) (d) Tyr-Tyr-T -Cys-Pro-Gly-Gln-Pro-Phe-Asp-Pro-Ala-T -Gly- Pro; (SEQ ID No. 123) (e) Asp-Ile-Gly-Ser-Glu-Ser-Thr-Glu-Asp-Gln-Gln-Xaa-Ala-Val; (SEQ ID No. 124) (f) Ala-Glu-Glu-Ser-Ile-Ser-Thr-Xaa-Glu-Xaa-Ile-Val-Pro; (SEQ ID No. 125) (g) Asp-Pro-Glu-Pro-Ala-Pro-Pro-Val-Pro-Thr-Thr-Ala-Ala-Ser- Pro-Pro-Ser; (SEQ ID No. 126) (h) Ala-Pro-Lys-Thr-Tyr-Xaa-Glu-Glu-Leu-Lys-Gly-Thr-Asp-Thr- Gly; (SEQ ID No. 127) (i) Asp-Pro-Ala-Ser-Ala-Pro-Asp-Val-Pro-Thr-Ala-Ala-Gln-Leu- Thr-Ser-Leu-Leu-Asn-Ser-Leu-Ala-Asp-Pro-Asn-Nal-Ser-Phe- Ala-Asn; (SEQ ID No. 128) (j) Xaa-Asp-Ser-Glu-Lys-Ser-Ala-Thr-Ile-Lys-Val-Thr-Asp-Ala- Ser; (SEQ ID No. 134) (k) Ala-Gly-Asp-Thr-Xaa-Ile-Tyr-Ile-Val-Gly-Asn-Leu-Thr-Ala- Asp; (SEQ ID No. 135) or (1) Ala-Pro-Glu-Ser-Gly-Ala-Gly-Leu-Gly-Gly-Thr-Val-Gln-Ala- Gly; (SEQ ID No. 136) wherein Xaa may be any amino acid. In a related aspect, polypeptides are provided comprising an immunogenic portion of an M. tuberculosis antigen, or a variant of such an antigen that differs only in conservative substitutions and/or modifications, the antigen having one ofthe following N-terminal sequences: (m) Xaa-Tyr-Ile-Ala-Tyr-Xaa-Thr-Thr-Ala-Gly-Ile-Nal-Pro-Gly-Lys- Ue-Asn-Val-His-Leu-Val; (SEQ ID No. 137) or (n) Asp-Pro-Pro-Asp-Pro-His-Gln-Xaa-Asp-Met-Thr-Lys-Gly-Tyr- Tyr-Pro-Gly-Gly-Arg-Arg-Xaa-Phe; (SEQ ID No. 129) wherein Xaa may be any amino acid. In another embodiment, the antigen comprises an amino acid sequence encoded by a DNA sequence selected from the group consisting of the sequences recited in SEQ ID Nos.: 1, 2, 4-10, 13-25, 52, 99 and 101, the complements of said sequences, and DNA sequences that hybridize to a sequence recited in SEQ ID Nos.: 1, 2, 4-10, 13-25, 52, 99 and 101 or a complement thereof under moderately stringent conditions. In a related aspect, the polypeptides comprise an immunogenic portion of a M. tuberculosis antigen, or a variant of such an antigen that differs only in conservative substitutions and/or modifications, wherein the antigen comprises an amino acid sequence encoded by a DNA sequence selected from the group consisting of the sequences recited in SEQ ID Nos.: 26-51, the complements of said sequences, and DNA sequences that hybridize to a sequence recited in SEQ ID Nos.: 26-51 or a complement thereof under moderately stringent conditions. In related aspects, DNA sequences encoding the above polypeptides, expression vectors comprising these DNA sequences and host cells transformed or transfected with such expression vectors are also provided. In another aspect, the present invention provides fusion proteins comprising a first and a second inventive polypeptide or, alternatively, an inventive polypeptide and a known M. tuberculosis antigen. Within other aspects, the present invention provides pharmaceutical compositions that comprise one or more ofthe above polypeptides, or a DNA molecule encoding such polypeptides, and a physiologically acceptable carrier. The invention also provides vaccines comprising one or more of the polypeptides as described above and a non-specific immune response enhancer, together with vaccines comprising one or more DNA sequences encoding such polypeptides and a non-specific immune response enhancer. In yet another aspect, methods are provided for inducing protective immunity in a patient, comprising administering to a patient an effective amount of one or more ofthe above polypeptides. In further aspects of this invention, methods and diagnostic kits are provided for detecting tuberculosis in a patient. The methods comprise contacting dermal cells of a patient with one or more of the above polypeptides and detecting an immune response on the patient's skin. The diagnostic kits comprise one or more ofthe above polypeptides in combination with an apparatus sufficient to contact the polypeptide with the dermal cells of a patient. These and other aspects of the present invention will become apparent upon reference to the following detailed description and attached drawings. All references disclosed herein are hereby incorporated by reference in their entirety as if each was incorporated individually. Brief Description ofthe Drawings and Sequence Identifiers Figure IA and B illustrate the stimulation of proliferation and interferon- γ production in T cells derived from a first and a second M. tuberculosis-hnmane donor, respectively, by the 14 Kd, 20 Kd and 26 Kd antigens described in Example 1. Figure 2 illustrates the stimulation of proliferation and interferon-γ production in T cells derived from an M. tuberculosis-immυne individual by the two representative polypeptides TbRa3 and TbRa9. SEQ. ID NO. 1 is the DNA sequence of TbRal . SEQ. ID NO. 2 is the DNA sequence of TbRal 0. SEQ. ID NO. 3 is the DNA sequence of TbRal 1. SEQ. ID NO. 4 is the DNA sequence of TbRal 2. SEQ. ID NO. 5 is the DNA sequence of TbRal 3. SEQ. ID NO. 6 is the DNA sequence of TbRal 6. SEQ. ID NO. 7 is the DNA sequence of TbRal 7. SEQ. ID NO. 8 is the DNA sequence of TbRal 8. SEQ. ID NO. 9 is the DNA sequence of TbRal 9. SEQ. ID NO. 10 is the DNA sequence of TbRa24. SEQ. ID NO. 11 is the DNA sequence of TbRa26. SEQ. ID NO. 12 is the DNA sequence of TbRa28. SEQ. ID NO. 13 is the DNA sequence of TbRa29. SEQ. ID NO. 14 is the DNA sequence of TbRa2A. SEQ. ID NO. 15 is the DNA sequence of TbRa3. SEQ. ID NO. 16 is the DNA sequence of TbRa32. SEQ. ID NO. 17 is the DNA sequence of TbRa35. SEQ. ID NO. 18 is the DNA sequence of TbRa36. SEQ. ID NO. 19 is the DNA sequence of TbRa4. SEQ. ID NO. 20 is the DNA sequence of TbRa9. SEQ. ID NO. 21 is the DNA sequence of TbRaB. SEQ. ID NO. 22 is the DNA sequence of TbRaC. SEQ. ID NO. 23 is the DNA sequence of TbRaD. SEQ. ID NO. 24 is the DNA sequence of YYWCPG. SEQ. ID NO. 25 is the DNA sequence of AAMK. SEQ. ID NO. 26 is the DNA sequence of TbL-23. SEQ. ID NO. 27 is the DNA sequence of TbL-24. SEQ. ID NO. 28 is the DNA sequence of TbL-25. SEQ. ID NO. 29 is the DNA sequence of TbL-28. SEQ. ID NO. 30 is the DNA sequence of TbL-29. SEQ. ID NO. 31 is the DNA sequence of TbH-5. SEQ. ID NO. 32 is the DNA sequence of TbH-8. SEQ. ID NO. 33 is the DNA sequence of TbH-9. SEQ. ID NO. 34 is the DNA sequence of TbM-1. SEQ. ID NO. 35 is the DNA sequence of TbM-3. SEQ. ID NO. 36 is the DNA sequence of TbM-6. SEQ. ID NO. 37 is the DNA sequence of TbM-7. SEQ. ID NO. 38 is the DNA sequence of TbM-9. SEQ. ID NO. 39 is the DNA sequence of TbM-12. SEQ. ID NO. 40 is the DNA sequence of TbM-13. SEQ. ID NO. 41 is the DNA sequence of TbM-14. SEQ. ID NO. 42 is the DNA sequence of TbM-15. SEQ. ID NO. 43 is the DNA sequence of TbH-4. SEQ. ID NO. 44 is the DNA sequence of TbH-4-FWD. SEQ. ID NO. 45 is the DNA sequence of TbH-12. SEQ. ID NO. 46 is the DNA sequence of Tb38-1. SEQ. ID NO. 47 is the DNA sequence of Tb38-4. SEQ. ID NO. 48 is the DNA sequence of TbL-17. SEQ. ID NO. 49 is the DNA sequence of TbL-20. SEQ. ID NO. 50 is the DNA sequence of TbL-21. SEQ. ID NO. 51 is the DNA sequence of TbH-16. SEQ. ID NO. 52 is the DNA sequence of DPEP. SEQ. ID NO. 53 is the deduced amino acid sequence of DPEP. SEQ. ID NO. 54 is the protein sequence of DPN Ν-terminal Antigen. SEQ. ID NO. 55 is the protein sequence of ANGS Ν-terminal Antigen. SEQ. ID NO. 56 is the protein sequence of AAMK N-terminal Antigen. SEQ. ID NO. 57 is the protein sequence of YYWC N-terminal Antigen. SEQ. ID NO. 58 is the protein sequence of DIGS N-terminal Antigen. SEQ. ID NO. 59 is the protein sequence of AEES N-terminal Antigen. SEQ. ID NO. 60 is the protein sequence of DPEP N-terminal Antigen. SEQ. ID NO. 61 is the protein sequence of APKT N-terminal Antigen. SEQ. ID NO. 62 is the protein sequence of DPAS N-terminal Antigen. SEQ. ID NO. 63 is the deduced amino acid sequence of TbRal. SEQ. ID NO. 64 is the deduced amino acid sequence of TbRal 0. SEQ. ID NO. 65 is the deduced amino acid sequence of TbRal 1. SEQ. ID NO. 66 is the deduced amino acid sequence of TbRal2. SEQ. ID NO. 67 is the deduced amino acid sequence of TbRal 3. SEQ. ID NO. 68 is the deduced amino acid sequence of TbRal 6. SEQ. ID NO. 69 is the deduced amino acid sequence of TbRal 7. SEQ. ID NO. 70 is the deduced amino acid sequence of TbRal 8. SEQ. ID NO. 71 is the deduced amino acid sequence of TbRal 9. SEQ. ID NO. 72 is the deduced amino acid sequence of TbRa24. SEQ. ID NO. 73 is the deduced amino acid sequence of TbRa26. SEQ. ID NO. 74 is the deduced amino acid sequence of TbRa28. SEQ. ID NO. 75 is the deduced amino acid sequence of TbRa29. SEQ. ID NO. 76 is the deduced amino acid sequence of TbRa2A. SEQ. ID NO. 77 is the deduced amino acid sequence of TbRa3. SEQ. ID NO. 78 is the deduced amino acid sequence of TbRa32. SEQ. ID NO. 79 is the deduced amino acid sequence of TbRa35. SEQ. ID NO. 80 is the deduced amino acid sequence of TbRa36. SEQ. ID NO. 81 is the deduced amino acid sequence of TbRa4. SEQ. ID NO. 82 is the deduced amino acid sequence of TbRa9. SEQ. ID NO. 83 is the deduced amino acid sequence of TbRaB. SEQ. ID NO. 84 is the deduced amino acid sequence of TbRaC. SEQ. ID NO. 85 is the deduced amino acid sequence of TbRaD. SEQ. ID NO. 86 is the deduced amino acid sequence of YYWCPG. SEQ. ID NO. 87 is the deduced amino acid sequence of TbAAMK. SEQ. ID NO. 88 is the deduced amino acid sequence of Tb38-1. SEQ. ID NO. 89 is the deduced amino acid sequence of TbH-4. SEQ. ID NO. 90 is the deduced amino acid sequence of TbH-8. SEQ. ID NO. 91 is the deduced amino acid sequence of TbH-9. SEQ. ID NO. 92 is the deduced amino acid sequence of TbH-12. SEQ. ID NO. 93 is the amino acid sequence of Tb38-1 Peptide 1. SEQ. ID NO. 94 is the amino acid sequence of Tb38-1 Peptide 2. SEQ. ID NO. 95 is the amino acid sequence of Tb38-1 Peptide 3. SEQ. ID NO. 96 is the amino acid sequence of Tb38-1 Peptide 4. SEQ. ID NO. 97 is the amino acid sequence of Tb38-1 Peptide 5. SEQ. ID NO. 98 is the amino acid sequence of Tb38-1 Peptide 6. SEQ. ID NO. 99 is the DNA sequence of DPAS. SEQ. ID NO. 100 s the deduced amino acid sequence of DPAS. SEQ. ID NO.101 s the DNA sequence of DPV. SEQ. ID NO.102 s the deduced amino acid sequence of DPV. SEQ. ID NO.103 s the DNA sequence of ESAT-6. SEQ. ID NO.104 s the deduced amino acid sequence of ESAT-6. SEQ. ID NO.105 s the DNA sequence of TbH-8-2. SEQ. ID NO.106 s the DNA sequence of TbH-9FL. SEQ. ID NO.107 s the deduced amino acid sequence of TbH-9FL. SEQ. ID NO.108 s the DNA sequence of TbH-9-1. SEQ. ID NO.109 s the deduced amino acid sequence of TbH-9-1. SEQ. ID NO.110 s the DNA sequence of TbH-9-4. SEQ. ID NO.111 s the deduced amino acid sequence of TbH-9-4. SEQ. ID NO.112 s the DNA sequence of Tb38-1F2 IN. SEQ. ID NO. 113 is the DNA sequence of Tb38-2F2 RP. SEQ. ID NO. 114 is the deduced amino acid sequence of Tb37-FL. SEQ. ID NO. 115 is the deduced amino acid sequence of Tb38-IN. SEQ. ID NO. 116 is the DNA sequence of Tb38-1F3. SEQ. ID NO. 117 is the deduced amino acid sequence of Tb38-1F3. SEQ. ID NO. 118 is the DNA sequence of Tb38-1F5. SEQ. ID NO. 119 is the DNA sequence of Tb38-1F6. SEQ. ID NO. 120 is the deduced N-terminal amino acid sequence of DPV. SEQ. ID NO. 121 is the deduced N-terminal amino acid sequence of AVGS. SEQ. ID NO. 122 is the deduced N-terminal amino acid sequence of AAMK. SEQ. ID NO. 123 is the deduced N-terminal amino acid sequence of YYWC. SEQ. ID NO. 124 is the deduced N-terminal amino acid sequence of DIGS. SEQ. ID NO. 125 is the deduced N-terminal amino acid sequence of AEES. SEQ. ID NO. 126 is the deduced N-terminal amino acid sequence of DPEP. SEQ. ID NO. 127 is the deduced N-terminal amino acid sequence of APKT. SEQ. ID NO. 128 is the deduced amino acid sequence of DPAS. SEQ. ID NO. 129 is the protein sequence of DPPD N-terminal Antigen. SEQ ID NO. 130-133 are the protein sequences of four DPPD cyanogen bromide fragments. SEQ ID NO. 134 is the N-terminal protein sequence of XDS antigen. SEQ ID NO. 135 is the N-terminal protein sequence of AGD antigen. SEQ ID NO. 136 is the N-terminal protein sequence of APE antigen. SEQ ID NO. 137 is the N-terminal protein sequence of XYI antigen. Detailed Description ofthe Invention As noted above, the present invention is generally directed to compositions and methods for preventing, treating and diagnosing tuberculosis. The compositions of the subject invention include polypeptides that comprise at least one immunogenic portion of a M. tuberculosis antigen, or a variant of such an antigen that differs only in conservative substitutions and/or modifications. Polypeptides within the scope of the present invention include, but are not limited to, immunogenic soluble M. tuberculosis antigens. A "soluble M. tuberculosis antigen" is a protein of M. tuberculosis origin that is present in M. tuberculosis culture filtrate. As used herein, the term "polypeptide" encompasses amino acid chains of any length, including full length proteins (i.e., antigens), wherein the amino acid residues are linked by covalent peptide bonds. Thus, a polypeptide comprising an immunogenic portion of one of the above antigens may consist entirely of the immunogenic portion, or may contain additional sequences. The additional sequences may be derived from the native M. tuberculosis antigen or may be heterologous, and such sequences may (but need not) be immunogenic. "Immunogenic," as used herein, refers to the ability to elicit an immune response (e.g., cellular) in a patient, such as a human, and/or in a biological sample. In particular, antigens that are immunogenic (and immunogenic portions or other variants of such antigens) are capable of stimulating cell proliferation, interleukin-12 production and/or interferon-γ production in biological samples comprising one or more cells selected from the group of T cells, NK cells, B cells and macrophages, where the cells are derived from an M. tuberculosis-unmυne individual. Polypeptides comprising at least an immunogenic portion of one or more M. tuberculosis antigens may generally be used to detect tuberculosis or to induce protective immunity against tuberculosis in a patient. The compositions and methods of this invention also encompass variants of the above polypeptides. A "variant," as used herein, is a polypeptide that differs from the native antigen only in conservative substitutions and/or modifications, such that the ability of the polypeptide to induce an immune response is retained. Such variants may generally be identified by modifying one of the above polypeptide sequences, and evaluating the immunogenic properties of the modified polypeptide using, for example, the representative procedures described herein. A "conservative substitution" is one in which an amino acid is substituted for another amino acid that has similar properties, such that one skilled in the art of peptide chemistry would expect the secondary structure and hydropathic nature of the polypeptide to be substantially unchanged. In general, the following groups of amino acids represent conservative changes: (1) aia, pro, gly, glu, asp, gin, asn, ser, thr; (2) cys, ser, tyr, thr; (3) val, ile, leu, met, aia, phe; (4) lys, arg, his; and (5) phe, tyr, trp, his. Variants may also (or alternatively) be modified by, for example, the deletion or addition of amino acids that have minimal influence on the immunogenic properties, secondary structure and hydropathic nature ofthe polypeptide. For example, a polypeptide may be conjugated to a signal (or leader) sequence at the N-terminal end of the protein which co-translationally or post-translationally directs transfer of the protein. The polypeptide may also be conjugated to a linker or other sequence for ease of synthesis, purification or identification of the polypeptide (e.g., poly-His), or to enhance binding of the polypeptide to a solid support. For example, a polypeptide may be conjugated to an immunoglobulin Fc region. In a related aspect, combination polypeptides are disclosed. A "combination polypeptide" is a polypeptide comprising at least one of the above immunogenic portions and one or more additional immunogenic M. tuberculosis sequences, which are joined via a peptide linkage into a single amino acid chain. The sequences may be joined directly (i.e., with no intervening amino acids) or may be joined by way of a linker sequence (e.g., Gly-Cys-Gly) that does not significantly diminish the immunogenic properties ofthe component polypeptides. In general, M. tuberculosis antigens, and DNA sequences encoding such antigens, may be prepared using any of a variety of procedures. For example, soluble antigens may be isolated from M. tuberculosis culture filtrate by procedures known to those of ordinary skill in the art, including anion-exchange and reverse phase chromatography. Purified antigens are then evaluated for their ability to elicit an appropriate immune response (e.g., cellular) using, for example, the representative methods described herein. Immunogenic antigens may then be partially sequenced using techniques such as traditional Edman chemistry. See Edman and Berg, Eur. J. Biochem. 50:116-132, 1967. Immunogenic antigens may also be produced recombinantly using a DNA sequence that encodes the antigen, which has been inserted into an expression vector and expressed in an appropriate host. DNA molecules encoding soluble antigens may be isolated by screening an appropriate M. tuberculosis expression library with anti-sera (e.g., rabbit) raised specifically against soluble M. tuberculosis antigens. DNA sequences encoding antigens that may or may not be soluble may be identified by screening an appropriate M. tuberculosis genomic or cDNA expression library with sera obtained from patients infected with M. tuberculosis. Such screens may generally be performed using techniques well known to those of ordinary skill in the art, such as those described in Sambrook et al., Molecular Cloning: A Laboratory Manual, Cold Spring Harbor Laboratories, Cold Spring Harbor, NY, 1989. DNA sequences encoding soluble antigens may also be obtained by screening an appropriate M. tuberculosis cDNA or genomic DNA library for DNA sequences that hybridize to degenerate oligonucleotides derived from partial amino acid sequences of isolated soluble antigens. Degenerate oligonucleotide sequences for use in such a screen may be designed and synthesized, and the screen may be performed, as described (for example) in Sambrook et al., Molecular Cloning: A Laboratory Manual, Cold Spring Harbor Laboratories, Cold Spring Harbor, NY, 1989 (and references cited therein). Polymerase chain reaction (PCR) may also be employed, using the above oligonucleotides in methods well known in the art, to isolate a nucleic acid probe from a cDNA or genomic library. The library screen may then be performed using the isolated probe. Alternatively, genomic or cDNA libraries derived from M. tuberculosis may be screened directly using peripheral blood mononuclear cells (PBMCs) or T cell lines or clones derived from one or more M. tuberculosis-immυne individuals. In general, PBMCs and/or T cells for use in such screens may be prepared as described below. Direct library screens may generally be performed by assaying pools of expressed recombinant proteins for the ability to induce proliferation and/or interferon-γ production in T cells derived from an M. tuberculosis-immυne individual. Alternatively, potential T cell antigens may be first selected based on antibody reactivity, as described above. Regardless ofthe method of preparation, the antigens (and immunogenic portions thereof) described herein (which may or may not be soluble) have the ability to induce an immunogenic response. More specifically, the antigens have the ability to induce proliferation and/or cytokine production (Le., interferon-γ and/or interleukin-12 production) in T cells, NK cells, B cells and/or macrophages derived from an M. tuberculosis-immυne individual. The selection of cell type for use in evaluating an immunogenic response to a antigen will, of course, depend on the desired response. For example, interleukin-12 production is most readily evaluated using preparations containing B cells and/or macrophages. An M. tuberculosis-immυne individual is one who is considered to be resistant to the development of tuberculosis by virtue of having mounted an effective T cell response to M. tuberculosis (i.e., substantially free of disease symptoms). Such individuals may be identified based on a strongly positive (i.e., greater than about 10 mm diameter induration) intradermal skin test response to tuberculosis proteins (PPD) and an absence of any signs or symptoms of tuberculosis disease. T cells, NK cells, B cells and macrophages derived from M. tuberculosis- immυne individuals may be prepared using methods known to those of ordinary skill in the art. For example, a preparation of PBMCs (i.e., peripheral blood mononuclear cells) may be employed without further separation of component cells. PBMCs may generally be prepared, for example, using density centrifugation through Ficoll™ (Winthrop Laboratories, NY). T cells for use in the assays described herein may also be purified directly from PBMCs. Alternatively, an enriched T cell line reactive against mycobacterial proteins, or T cell clones reactive to individual mycobacterial proteins, may be employed. Such T cell clones may be generated by, for example, culturing PBMCs from M. tuberculosis-immυne individuals with mycobacterial proteins for a period of 2-4 weeks. This allows expansion of only the mycobacterial protein-specific T cells, resulting in a line composed solely of such cells. These cells may then be cloned and tested with individual proteins, using methods known to those of ordinary skill in the art, to more accurately define individual T cell specificity. In general, antigens that test positive in assays for proliferation and/or cytokine production (i.e., interferon-γ and/or interleukin-12 production) performed using T cells, NK cells, B cells and/or macrophages derived from an M. tuberculosis-immυne individual are considered immunogenic. Such assays may be performed, for example, using the representative procedures described below. Immunogenic portions of such antigens may be identified using similar assays, and may be present within the polypeptides described herein. The ability of a polypeptide (e.g., an immunogenic antigen, or a portion or other variant thereof) to induce cell proliferation is evaluated by contacting the cells (e.g., T cells and/or NK cells) with the polypeptide and measuring the proliferation of the cells. In general, the amount of polypeptide that is sufficient for evaluation of about IO 5 cells ranges from about lO ng/mL to about 100 μg/mL and preferably is about 10 μg/mL. The incubation of polypeptide with cells is typically performed at 37°C for about six days. Following incubation with polypeptide, the cells are assayed for a proliferative response, which may be evaluated by methods known to those of ordinary skill in the art, such as exposing cells to a pulse of radiolabeled thymidine and measuring the incorporation of label into cellular DNA. In general, a polypeptide that results in at least a three fold increase in proliferation above background (i.e., the proliferation observed for cells cultured without polypeptide) is considered to be able to induce proliferation. The ability of a polypeptide to stimulate the production of interferon-γ and/or interleukin-12 in cells may be evaluated by contacting the cells with the polypeptide and measuring the level of interferon-γ or interleukin-12 produced by the cells. In general, the amount of polypeptide that is sufficient for the evaluation of about IO 5 cells ranges from about lO ng/mL to about lOO μg/mL and preferably is about 10 μg/mL. The polypeptide may, but need not, be immobilized on a solid support, such as a bead or a biodegradable microsphere, such as those described in U.S. Patent Nos. 4,897,268 and 5,075,109. The incubation of polypeptide with the cells is typically performed at 37°C for about six days. Following incubation with polypeptide, the cells are assayed for interferon-γ and/or interleukin-12 (or one or more subunits thereof), which may be evaluated by methods known to those of ordinary skill in the art, such as an enzyme-linked immunosorbent assay (ELISA) or, in the case of IL-l 2 P70 subunit, a bioassay such as an assay measuring proliferation of T cells. In general, a polypeptide that results in the production of at least 50 pg of interferon-γ per mL of cultured supernatant (containing 10 0 5 T cells per mL) is considered able to stimulate the production of interferon-γ. A polypeptide that stimulates the production of at least 10 pg/mL of IL-l 2 P70 subunit, and or at least 100 pg/mL of IL-l 2 P40 subunit, per IO 5 macrophages or B cells (or per 3 x 10 5 PBMC) is considered able to stimulate the production of IL-l 2. In general, immunogenic antigens are those antigens that stimulate proliferation and/or cytokine production (i.e., interferon-γ and/or interleukin-12 production) in T cells, NK cells, B cells and/or macrophages derived from at least about 25% of M. tuberculosis-immυne individuals. Among these immunogenic antigens, polypeptides having superior therapeutic properties may be distinguished based on the magnitude of the responses in the above assays and based on the percentage of individuals for which a response is observed. In addition, antigens having superior therapeutic properties will not stimulate proliferation and/or cytokine production in vitro in cells derived from more than about 25% of individuals that are not M. tuberculosis-immυne, thereby eliminating responses that are not specifically due to M. tuberculosis-responsive cells. Those antigens that induce a response in a high percentage of T cell, NK cell, B cell and/or macrophage preparations from M. tuberculosis-immυne individuals (with a low incidence of responses in cell preparations from other individuals) have superior therapeutic properties. Antigens with superior therapeutic properties may also be identified based on their ability to diminish the severity of M. tuberculosis infection in experimental animals, when administered as a vaccine. Suitable vaccine preparations for use on experimental animals are described in detail below. Efficacy may be determined based on the ability ofthe antigen to provide at least about a 50% reduction in bacterial numbers and/or at least about a 40% decrease in mortality following experimental infection. Suitable experimental animals include mice, guinea pigs and primates. Antigens having superior diagnostic properties may generally be identified based on the ability to elicit a response in an intradermal skin test performed on an individual with active tuberculosis, but not in a test performed on an individual who is not infected with M. tuberculosis. Skin tests may generally be performed as described below, with a response of at least 5 mm induration considered positive. Immunogenic portions of the antigens described herein may be prepared and identified using well known techniques, such as those summarized in Paul, Fundamental Immunology, 3d ed., Raven Press, 1993, pp. 243-247 and references cited therein. Such techniques include screening polypeptide portions of the native antigen for immunogenic properties. The representative proliferation and cytokine production assays described herein may generally be employed in these screens. An immunogenic portion of a polypeptide is a portion that, within such representative assays, generates an immune response (e.g., proliferation, interferon-γ production and/or interleukin-12 production) that is substantially similar to that generated by the full length antigen. In other words, an immunogenic portion of an antigen may generate at least about 20%, and preferably about 100%, ofthe proliferation induced by the full length antigen in the model proliferation assay described herein. An immunogenic portion may also, or alternatively, stimulate the production of at least about 20%, and preferably about 100%, ofthe interferon-γ and/or interleukin-12 induced by the full length antigen in the model assay described herein. Portions and other variants of M. tuberculosis antigens may be generated by synthetic or recombinant means. Synthetic polypeptides having fewer than about 100 amino acids, and generally fewer than about 50 amino acids, may be generated using techniques well known to those of ordinary skill in the art. For example, such polypeptides may be synthesized using any of the commercially available solid-phase techniques, such as the Merrifϊeld solid-phase synthesis method, where amino acids are sequentially added to a growing amino acid chain. See Merrifϊeld, J. Am. Chem. Soc. •55:2149-2146, 1963. Equipment for automated synthesis of polypeptides is commercially available from suppliers such as Applied BioSystems, Inc., Foster City, CA, and may be operated according to the manufacturer's instructions. Variants of a native antigen may generally be prepared using standard mutagenesis techniques, such as oligonucleotide-directed site-specific mutagenesis. Sections of the DNA sequence may also be removed using standard techniques to permit preparation of truncated polypeptides. Recombinant polypeptides containing portions and/or variants of a native antigen may be readily prepared from a DNA sequence encoding the polypeptide using a variety of techniques well known to those of ordinary skill in the art. For example, supernatants from suitable host/vector systems which secrete recombinant protein into culture media may be first concentrated using a commercially available filter. Following concentration, the concentrate may be applied to a suitable purification matrix such as an affinity matrix or an ion exchange resin. Finally, one or more reverse phase HPLC steps can be employed to further purify a recombinant protein. Any of a variety of expression vectors known to those of ordinary skill in the art may be employed to express recombinant polypeptides of this invention. Expression may be achieved in any appropriate host cell that has been transformed or transfected with an expression vector containing a DNA molecule that encodes a recombinant polypeptide. Suitable host cells include prokaryotes, yeast and higher eukaryotic cells. Preferably, the host cells employed are E. coli, yeast or a mammalian cell line such as COS or CHO. The DNA sequences expressed in this manner may encode naturally occurring antigens, portions of naturally occurring antigens, or other variants thereof. In general, regardless of the method of preparation, the polypeptides disclosed herein are prepared in substantially pure form. Preferably, the polypeptides are at least about 80% pure, more preferably at least about 90% pure and most preferably at least about 99% pure. In certain preferred embodiments, described in detail below, the substantially pure polypeptides are incoφorated into pharmaceutical compositions or vaccines for use in one or more ofthe methods disclosed herein. In certain specific embodiments, the subject invention discloses polypeptides comprising at least an immunogenic portion of a soluble M. tuberculosis antigen having one of the following N-terminal sequences, or a variant thereof that differs only in conservative substitutions and/or modifications: (a) Asp-Pro- Val-Asp-Ala-Val-Ile-Asn-Thr-Thr-Cys-Asn-Tyr-Gly- Gln-Val-Val-Ala-Ala-Leu; (SEQ ID No. 120) (b) Ala-Val-Glu-Ser-Gly-Met-Leu-Ala-Leu-Gly-Thr-Pro-Ala-Pro- Ser; (SEQ ID No. 121) (c) Ala-Ala-Met-Lys-Pro-Arg-Thr-Gly-Asp-Gly-Pro-Leu-Glu-Ala- Ala-Lys-Glu-Gly-Arg; (SEQ ID No. 122) (d) Tyr-Tyr-Tφ-Cys-Pro-Gly-Gln-Pro-Phe-Asp-Pro-Ala-Tφ-Gly- Pro; (SEQ ID No. 123) (e) Asp-Ile-Gly-Ser-Glu-Ser-Thr-Glu-Asp-Gln-Gln-Xaa-Ala-Val; (SEQ ID No. 124) (f) Ala-Glu-Glu-Ser-Ile-Ser-Thr-Xaa-Glu-Xaa-Ile-Val-Pro; (SEQ ID No. 125) (g) Asp-Pro-Glu-Pro-Ala-Pro-Pro-Val-Pro-Thr-Ala-Ala-Ala-Ser- Pro-Pro-Ser; (SEQ ID No. 126) (h) Ala-Pro-Lys-Thr-Tyr-Xaa-Glu-Glu-Leu-Lys-Gly-Thr-Asp-Thr- Gly; (SEQ ID No. 127) (i) Asp-Pro-Ala-Ser-Ala-Pro-Asp-Val-Pro-Thr-Ala-Ala-Gln-Leu- Thr-Ser-Leu-Leu-Asn-Ser-Leu-Ala-Asp-Pro-Asn-Val-Ser-Phe- Ala-Asn; (SEQ ID No. 128) (j) Xaa-Asp-Ser-Glu-Lys-Ser-Ala-Thr-Ile-Lys-Val-Thr-Asp-Ala- Ser; (SEQ ID No. 134) (k) Ala-Gly-Asp-Thr-Xaa-Ile-Tyr-Ile-Val-Gly-Asn-Leu-Thr-Ala- Asp; (SEQ ID No. 135) or (1) Ala-Pro-Glu-Ser-Gly-Ala-Gly-Leu-Gly-Gly-Thr-Val-Gln-Ala- Gly; (SEQ ID No. 136) wherein Xaa may be any amino acid, preferably a cysteine residue. A DNA sequence encoding the antigen identified as (g) above is provided in SEQ ID No. 52, and the polypeptide encoded by SEQ ID No. 52 is provided in SEQ ID No. 53. A DNA sequence encoding the antigen defined as (a) above is provided in SEQ ID No. 101; its deduced amino acid sequence is provided in SEQ ID No. 102. A DNA sequence corresponding to antigen (d) above is provided in SEQ ID No. 24 a DNA sequence corresponding to antigen (c) is provided in SEQ ID No. 25 and a DNA sequence corresponding to antigen (i) is provided in SEQ ID No. 99; its deduced amino acid sequence is provided in SEQ ID No. 100. In a further specific embodiment, the subject invention discloses polypeptides comprising at least an immunogenic portion of an M. tuberculosis antigen having one ofthe following N-terminal sequences, or a variant thereof that differs only in conservative substitutions and/or modifications: (m) Xaa-Tyr-Ile-Ala-Tyr-Xaa-Thr-Thr-Ala-Gly-Ile-Val-Pro-Gly-Lys- Ile-Asn-Val-His-Leu-Val; (SEQ ID No 137) or (n) Asp-Pro-Pro-Asp-Pro-His-Gln-Xaa-Asp-Met-Thr-Lys-Gly-Tyr- Tyr-Pro-Gly-Gly-Arg-Arg-Xaa-Phe; (SEQ ID No. 129) wherein Xaa may be any amino acid, preferably a cysteine residue. In other specific embodiments, the subject invention discloses polypeptides comprising at least an immunogenic portion of a soluble M. tuberculosis antigen (or a variant of such an antigen) that comprises one or more of the amino acid sequences encoded by (a) the DNA sequences of SEQ ID Nos.: 1, 2, 4-10, 13-25 and 52; (b) the complements of such DNA sequences, or (c) DNA sequences substantially homologous to a sequence in (a) or (b). In further specific embodiments, the subject invention discloses polypeptides comprising at least an immunogenic portion of a M. tuberculosis antigen (or a variant of such an antigen), which may or may not be soluble, that comprises one or more of the amino acid sequences encoded by (a) the DNA sequences of SEQ ID Nos.: 26-51, (b) the complements of such DNA sequences or (c) DNA sequences substantially homologous to a sequence in (a) or (b). In the specific embodiments discussed above, the M. tuberculosis antigens include variants that are encoded by DNA sequences which are substantially homologous to one or more of DNA sequences specifically recited herein. "Substantial homology," as used herein, refers to DNA sequences that are capable of hybridizing under moderately stringent conditions. Suitable moderately stringent conditions include prewashing in a solution of 5X SSC, 0.5% SDS, 1.0 mM EDTA (pH 8.0); hybridizing at 50°C-65°C, 5X SSC, overnight or, in the case of cross-species homology at 45°C, 0.5X SSC; followed by washing twice at 65°C for 20 minutes with each of 2X, 0.5X and 0.2X SSC containing 0.1% SDS). Such hybridizing DNA sequences are also within the scope of this invention, as are nucleotide sequences that, due to code degeneracy, encode an immunogenic polypeptide that is encoded by a hybridizing DNA sequence. In a related aspect, the present invention provides fusion proteins comprising a first and a second inventive polypeptide or, alternatively, a polypeptide of the present invention and a known M tuberculosis antigen, such as the 38 kD antigen described above or ESAT-6 (SEQ ID Nos. 103 and 104), together with variants of such fusion proteins. The fusion proteins of the present invention may also include a linker peptide between the first and second polypeptides. A DNA sequence encoding a fusion protein of the present invention is constructed using known recombinant DNA techniques to assemble separate DNA sequences encoding the first and second polypeptides into an appropriate expression vector. The 3' end of a DNA sequence encoding the first polypeptide is ligated, with or without a peptide linker, to the 5' end of a DNA sequence encoding the second polypeptide so that the reading frames of the sequences are in phase to permit mRNA translation of the two DNA sequences into a single fusion protein that retains the biological activity of both the first and the second polypeptides. A peptide linker sequence may be employed to separate the first and the second polypeptides by a distance sufficient to ensure that each polypeptide folds into its secondary and tertiary structures. Such a peptide linker sequence is incoφorated into the fusion protein using standard techniques well known in the art. Suitable peptide linker sequences may be chosen based on the following factors: (1) their ability to adopt a flexible extended conformation; (2) their inability to adopt a secondary structure that could interact with functional epitopes on the first and second polypeptides; and (3) the lack of hydrophobic or charged residues that might react with the polypeptide functional epitopes. Preferred peptide linker sequences contain Gly, Asn and Ser residues. Other near neutral amino acids, such as Thr and Ala may also be used in the linker sequence. Amino acid sequences which may be usefully employed as linkers include those disclosed in Maratea et al., Gene 40:39-46, 1985; Muφhy et al., Proc. Natl. Acad. Sci. USA 55:8258-8262, 1986; U.S. Patent No. 4,935,233 and U.S. Patent No. 4,751,180. The linker sequence may be from 1 to about 50 amino acids in length. Peptide sequences are not required when the first and second polypeptides have non¬ essential N-terminal amino acid regions that can be used to separate the functional domains and prevent steric interference. The ligated DNA sequences are operably linked to suitable transcriptional or translational regulatory elements. The regulatory elements responsible for expression of DNA are located only 5' to the DNA sequence encoding the first polypeptides. Similarly, stop codons require to end translation and transcription termination signals are only present 3' to the DNA sequence encoding the second polypeptide. In another aspect, the present invention provides methods for using one or more ofthe above polypeptides or fusion proteins (or DNA molecules encoding such polypeptides) to induce protective immunity against tuberculosis in a patient. As used herein, a "patient" refers to any warm-blooded animal, preferably a human. A patient may be afflicted with a disease, or may be free of detectable disease and/or infection. In other words, protective immunity may be induced to prevent or treat tuberculosis. In this aspect, the polypeptide, fusion protein or DNA molecule is generally present within a pharmaceutical composition and/or a vaccine. Pharmaceutical compositions may comprise one or more polypeptides, each of which may contain one or more of the above sequences (or variants thereof), and a physiologically acceptable carrier. Vaccines may comprise one or more of the above polypeptides and a non-specific immune response enhancer, such as an adjuvant or a liposome (into which the polypeptide is incoφorated). Such pharmaceutical compositions and vaccines may also contain other M. tuberculosis antigens, either incoφorated into a combination polypeptide or present within a separate polypeptide. Alternatively, a vaccine may contain DNA encoding one or more polypeptides as described above, such that the polypeptide is generated in situ. In such vaccines, the DNA may be present within any of a variety of delivery systems known to those of ordinary skill in the art, including nucleic acid expression systems, bacterial and viral expression systems. Appropriate nucleic acid expression systems contain the necessary DNA sequences for expression in the patient (such as a suitable promoter and terminating signal). Bacterial delivery systems involve the administration of a bacterium (such as Bacillus-Calmette-Guerriή) that expresses an immunogenic portion of the polypeptide on its cell surface. In a preferred embodiment, the DNA may be introduced using a viral expression system (e.g., vaccinia or other pox virus, retrovirus, or adenovirus), which may involve the use of a non-pathogenic (defective), replication competent virus. Techniques for incoφorating DNA into such expression systems are well known to those of ordinary skill in the art. The DNA may also be "naked," as described, for example, in Ulmer et al., Science 259:1745-1749, 1993 and reviewed by Cohen, Science 259:1691-1692, 1993. The uptake of naked DNA may be increased by coating the DNA onto biodegradable beads, which are efficiently transported into the cells. In a related aspect, a DNA vaccine as described above may be administered simultaneously with or sequentially to either a polypeptide of the present invention or a known M. tuberculosis antigen, such as the 38 kD antigen described above. For example, administration of DNA encoding a polypeptide of the present invention, either "naked" or in a delivery system as described above, may be followed by administration of an antigen in order to enhance the protective immune effect of the vaccine. Routes and frequency of administration, as well as dosage, will vary from individual to individual and may parallel those currently being used in immunization using BCG. In general, the pharmaceutical compositions and vaccines may be administered by injection (e.g., intracutaneous, intramuscular, intravenous or subcutaneous), intranasally (e.g., by aspiration) or orally. Between 1 and 3 doses may be administered for a 1-36 week period. Preferably, 3 doses are administered, at intervals of 3-4 months, and booster vaccinations may be given periodically thereafter. Alternate protocols may be appropriate for individual patients. A suitable dose is an amount of polypeptide or DNA that, when administered as described above, is capable of raising an immune response in an immunized patient sufficient to protect the patient from M. tuberculosis infection for at least 1-2 years. In general, the amount of polypeptide present in a dose (or produced in situ by the DNA in a dose) ranges from about 1 pg to about 100 mg per kg of host, typically from about 10 pg to about 1 mg, and preferably from about 100 pg to about 1 μg. Suitable dose sizes will vary with the size ofthe patient, but will typically range from about 0.1 mL to about 5 mL. While any suitable carrier known to those of ordinary skill in the art may be employed in the pharmaceutical compositions of this invention, the type of carrier will vary depending on the mode of administration. For parenteral administration, such as subcutaneous injection, the carrier preferably comprises water, saline, alcohol, a fat, a wax or a buffer. For oral administration, any of the above carriers or a solid carrier, such as mannitol. lactose, starch, magnesium stearate, sodium saccharine, talcum, cellulose, glucose, sucrose, and magnesium carbonate, may be employed. Biodegradable microspheres (e.g., poly lactic galactide) may also be employed as carriers for the pharmaceutical compositions of this invention. Suitable biodegradable microspheres are disclosed, for example, in U.S. Patent Nos. 4,897,268 and 5,075,109. Any of a variety of adjuvants may be employed in the vaccines of this invention to nonspecifically enhance the immune response. Most adjuvants contain a substance designed to protect the antigen from rapid catabolism, such as aluminum hydroxide or mineral oil, and a nonspecific stimulator of immune responses, such as lipid A, Bortadella pertussis or Mycobacterium tuberculosis. Suitable adjuvants are commercially available as, for example, Freund's Incomplete Adjuvant and Freund's Complete Adjuvant (Difco Laboratories) and Merck Adjuvant 65 (Merck and Company, Inc., Rahway, NJ). Other suitable adjuvants include alum, biodegradable microspheres, monophosphoryl lipid A and quil A. In another aspect, this invention provides methods for using one or more of the polypeptides described above to diagnose tuberculosis using a skin test. As used herein, a "skin test" is any assay performed directly on a patient in which a delayed-type hypersensitivity (DTH) reaction (such as swelling, reddening or dermatitis) is measured following intradermal injection of one or more polypeptides as described above. Such injection may be achieved using any suitable device sufficient to contact the polypeptide or polypeptides with dermal cells of the patient, such as a tuberculin syringe or 1 mL syringe. Preferably, the reaction is measured at least 48 hours after injection, more preferably 48-72 hours. The DTH reaction is a cell-mediated immune response, which is greater in patients that have been exposed previously to the test antigen (i.e., the immunogenic portion of the polypeptide employed, or a variant thereof)- The response may be measured visually, using a ruler. In general, a response that is greater than about 0.5 cm in diameter, preferably greater than about 1.0 cm in diameter, is a positive response, indicative of tuberculosis infection, which may or may not be manifested as an active disease. The polypeptides of this invention are preferably formulated, for use in a skin test, as pharmaceutical compositions containing a polypeptide and a physiologically acceptable carrier, as described above. Such compositions typically contain one or more ofthe above polypeptides in an amount ranging from about 1 μg to about 100 μg, preferably from about 10 μg to about 50 μg in a volume of 0.1 mL. Preferably, the carrier employed in such pharmaceutical compositions is a saline solution with appropriate preservatives, such as phenol and/or Tween 80™. In a preferred embodiment, a polypeptide employed in a skin test is of sufficient size such that it remains at the site of injection for the duration ofthe reaction period. In general, a polypeptide that is at least 9 amino acids in length is sufficient. The polypeptide is also preferably broken down by macrophages within hours of injection to allow presentation to T-cells. Such polypeptides may contain repeats of one or more of the above sequences and/or other immunogenic or nonimmunogenic sequences. The following Examples are offered by way of illustration and not by way of limitation. EXAMPLES EXAMPLE 1 PURIFICATION AND CHARACTERIZATION OF POLYPEPTIDES FROM M. TUBERCULOSIS CULTURE FILTRATE This example illustrates the preparation of M. tuberculosis soluble polypeptides from culture filtrate. Unless otherwise noted, all percentages in the following example are weight per volume. M. tuberculosis (either H37Ra, ATCC No. 25177, or H37Rv, ATCC No. 25618) was cultured in sterile GAS media at 37°C for fourteen days. The media was then vacuum filtered (leaving the bulk of the cells) through a 0.45 μ filter into a sterile 2.5 L bottle. The media was next filtered through a 0.2 μ filter into a sterile 4 L bottle and NaN 3 was added to the culture filtrate to a concentration of 0.04%. The bottles were then placed in a 4°C cold room. The culture filtrate was concentrated by placing the filtrate in a 12 L reservoir that had been autoclaved and feeding the filtrate into a 400 ml Amicon stir cell which had been rinsed with ethanol and contained a 10,000 kDa MWCO membrane. The pressure was maintained at 60 psi using nitrogen gas. This procedure reduced the 12 L volume to approximately 50 ml. The culture filtrate was dialyzed into 0.1% ammonium bicarbonate using a 8,000 kDa MWCO cellulose ester membrane, with two changes of ammonium bicarbonate solution. Protein concentration was then determined by a commercially available BCA assay (Pierce, Rockford, IL). The dialyzed culture filtrate was then lyophilized, and the polypeptides resuspended in distilled water. The polypeptides were dialyzed against 0.01 mM 1,3 bis[tris(hydroxymethyl)-methylamino]propane, pH 7.5 (Bis-Tris propane buffer), the initial conditions for anion exchange chromatography. Fractionation was performed using gel profusion chromatography on a POROS 146 II Q/M anion exchange column 4.6 mm x 100 mm (Perseptive BioSystems, Framingham, MA) equilibrated in 0.01 mM Bis-Tris propane buffer pH 7.5. Polypeptides were eluted with a linear 0-0.5 M NaCl gradient in the above buffer system. The column eluent was monitored at a wavelength of 220 nm. The pools of polypeptides eluting from the ion exchange column were dialyzed against distilled water and lyophilized. The resulting material was dissolved in 0.1% trifluoroacetic acid (TFA) pH 1.9 in water, and the polypeptides were purified on a Delta-Pak C18 column (Waters, Milford, MA) 300 Angstrom pore size, 5 micron particle size (3.9 x 150 mm). The polypeptides were eluted from the column with a linear gradient from 0-60% dilution buffer (0.1% TFA in acetonitrile). The flow rate was 0.75 ml/minute and the HPLC eluent was monitored at 214 nm. Fractions containing the eluted polypeptides were collected to maximize the purity of the individual samples. Approximately 200 purified polypeptides were obtained. The purified polypeptides were then screened for the ability to induce T- cell proliferation in PBMC preparations. The PBMCs from donors known to be PPD skin test positive and whose T-cells were shown to proliferate in response to PPD and crude soluble proteins from MTB were cultured in medium comprising RPMI 1640 supplemented with 10% pooled human serum and 50 μg/ml gentamicin. Purified polypeptides were added in duplicate at concentrations of 0.5 to 10 μg/mL. After six days of culture in 96-well round-bottom plates in a volume of 200 μl, 50 μl of medium was removed from each well for determination of IFN-γ levels, as described below. The plates were then pulsed with 1 μCi/well of tritiated thymidine for a further 18 hours, harvested and tritium uptake determined using a gas scintillation counter. Fractions that resulted in proliferation in both replicates three fold greater than the proliferation observed in cells cultured in medium alone were considered positive. IFN-γ was measured using an enzyme-linked immunosorbent assay (ELISA). ELISA plates were coated with a mouse monoclonal antibody directed to human IFN-γ (PharMingen, San Diego, CA) in PBS for four hours at room temperature. Wells were then blocked with PBS containing 5% (W/V) non-fat dried milk for 1 hour at room temperature. The plates were then washed six times in PBS/0.2% TWEEN-20 and samples diluted 1 :2 in culture medium in the ELISA plates were incubated overnight at room temperature. The plates were again washed and a polyclonal rabbit anti-human IFN-γ serum diluted 1:3000 in PBS/10% normal goat serum was added to each well. The plates were then incubated for two hours at room temperature, washed and horseradish peroxidase-coupled anti-rabbit IgG (Sigma Chemical So., St. Louis, MO) was added at a 1 :2000 dilution in PBS/5% non-fat dried milk. After a further two hour incubation at room temperature, the plates were washed and TMB substrate added. The reaction was stopped after 20 min with 1 N sulfuric acid. Optical density was determined at 450 nm using 570 nm as a reference wavelength. Fractions that resulted in both replicates giving an OD two fold greater than the mean OD from cells cultured in medium alone, plus 3 standard deviations, were considered positive. For sequencing, the polypeptides were individually dried onto Biobrene™ (Perkin Elmer/ Applied BioSystems Division, Foster City, CA) treated glass fiber filters. The filters with polypeptide were loaded onto a Perkin Elmer/Applied BioSystems Division Procise 492 protein sequencer. The polypeptides were sequenced from the amino terminal and using traditional Edman chemistry. The amino acid sequence was determined for each polypeptide by comparing the retention time of the PTH amino acid derivative to the appropriate PTH derivative standards. Using the procedure described above, antigens having the following N-terminal sequences were isolated: (a) Asp-Pro-Val-Asp-Ala-Val-Ile-Asn-Thr-Thr-Xaa-Asn-Tyr-Gly- Gln-Val-Val-Ala-Ala-Leu; (SEQ ID No. 54) (b) Ala-Val-Glu-Ser-Gly-Met-Leu-Ala-Leu-Gly-Thr-Pro-Ala-Pro- Ser; (SEQ ID No. 55) (c) Ala-Ala-Met-Lys-Pro-Arg-Thr-Gly-Asp-Gly-Pro-Leu-Glu-Ala- Ala-Lys-Glu-Gly-Arg; (SEQ ID No. 56) (d) Tyr-Tyr-Tφ-Cys-Pro-Gly-Gln-Pro-Phe-Asp-Pro-Ala-Tφ-Gly- Pro; (SEQ ID No. 57) (e) Asp-Ile-Gly-Ser-Glu-Ser-Thr-Glu-Asp-Gln-Gln-Xaa-Ala-Val; (SEQ ID No. 58) (f) Ala-Glu-Glu-Ser-Ile-Ser-Thr-Xaa-Glu-Xaa-Ile-Val-Pro; (SEQ ID No. 59) (g) Asp-Pro-Glu-Pro-Ala-Pro-Pro-Val-Pro-Thr-Ala-Ala-Ala-Ala- Pro-Pro-Ala; (SEQ ID No. 60) and (h) Ala-Pro-Lys-Thr-Tyr-Xaa-Glu-Glu-Leu-Lys-Gly-Thr-Asp-Thr- Gly; (SEQ ID No. 61) wherein Xaa may be any amino acid. An additional antigen was isolated employing a microbore HPLC purification step in addition to the procedure described above. Specifically, 20 μl of a fraction comprising a mixture of antigens from the chromatographic purification step previously described, was purified on an Aquapore C 18 column (Perkin Elmer/ Applied Biosystems Division, Foster City, CA) with a 7 micron pore size, column size 1 mm x 100 mm, in a Perkin Elmer/ Applied Biosystems Division Model 172 HPLC. Fractions were eluted from the column with a linear gradient of 1%/minute of acetonitrile (containing 0.05% TFA) in water (0.05% TFA) at a flow rate of 80 μl/minute. The eluent was monitored at 250 nm. The original fraction was separated into 4 major peaks plus other smaller components and a polypeptide was obtained which was shown to have a molecular weight of 12.054 Kd (by mass spectrometry) and the following N- terminal sequence: (i) Asp-Pro-Ala-Ser-Ala-Pro-Asp-Val-Pro-Thr-Ala-Ala-Gln-Gln- Thr-Ser-Leu-Leu-Asn-Asn-Leu-Ala-Asp-Pro-Asp-Val-Ser-Phe- Ala-Asp (SEQ ID No. 62). This polypeptide was shown to induce proliferation and IFN-γ production in PBMC preparations using the assays described above. Additional soluble antigens were isolated from M. tuberculosis culture filtrate as follows. M. tuberculosis culture filtrate was prepared as described above. Following dialysis against Bis-Tris propane buffer, at pH 5.5, fractionation was performed using anion exchange chromatography on a Poros QE column 4.6 x 100 mm (Perseptive Biosystems) equilibrated in Bis-Tris propane buffer pH 5.5. Polypeptides were eluted with a linear 0-1.5 M NaCl gradient in the above buffer system at a flow rate of 10 ml/min. The column eluent was monitored at a wavelength of 214 nm. The fractions eluting from the ion exchange column were pooled and subjected to reverse phase chromatography using a Poros R2 column 4.6 x 100 mm (Perseptive Biosystems). Polypeptides were eluted from the column with a linear gradient from 0-100% acetonitrile (0.1% TFA) at a flow rate of 5 ml min. The eluent was monitored at 214 nm. Fractions containing the eluted polypeptides were lyophilized and resuspended in 80 μl of aqueous 0.1% TFA and further subjected to reverse phase chromatography on a Vydac C4 column 4.6 x 150 mm (Western Analytical, Temecula, CA) with a linear gradient of 0-100% acetonitrile (0.1% TFA) at a flow rate of 2 ml/min. Eluent was monitored at 214 nm. The fraction with biological activity was separated into one major peak plus other smaller components. Western blot of this peak onto PVDF membrane revealed three major bands of molecular weights 14 Kd, 20 Kd and 26 Kd. These polypeptides were determined to have the following N-terminal sequences, respectively: (j) Xaa-Asp-Ser-Glu-Lys-Ser-Ala-Thr-Ile-Lys-Val-Thr-Asp-Ala- Ser; (SEQ ID No. 134) (k) Ala-Gly-Asp-Thr-Xaa-Ile-Tyr-Ile-Val-Gly-Asn-Leu-Thr-Ala- Asp; (SEQ ID No. 135) and (1) Ala-Pro-Glu-Ser-Gly-Ala-Gly-Leu-Gly-Gly-Thr-Val-Gln-Ala- Gly; (SEQ ID No. 136), wherein Xaa may be any amino acid. Using the assays described above, these polypeptides were shown to induce proliferation and IFN-γ production in PBMC preparations. Figs. IA and B show the results of such assays using PBMC preparations from a first and a second donor, respectively. DNA sequences that encode the antigens designated as (a), (c), (d) and (g) above were obtained by screening a genomic M. tuberculosis library using 32 P end labeled degenerate oligonucleotides corresponding to the N-terminal sequence and containing M. tuberculosis codon bias. The screen performed using a probe corresponding to antigen (a) above identified a clone having the sequence provided in SEQ ID No. 101. The polypeptide encoded by SEQ ID No. 101 is provided in SEQ ID No. 102. The screen performed using a probe corresponding to antigen (g) above identified a clone having the sequence provided in SEQ ID No. 52. The polypeptide encoded by SEQ ID No. 52 is provided in SEQ ID No. 53. The screen performed using a probe corresponding to antigen (d) above identified a clone having the sequence provided in SEQ ID No. 24, and the screen performed with a probe corresponding to antigen (c) identified a clone having the sequence provided in SEQ ID No: 25. The above amino acid sequences were compared to known amino acid sequences in the gene bank using the DNA STAR system. The database searched contains some 173,000 proteins and is a combination ofthe Swiss, PIR databases along with translated protein sequences (Version 87). No significant homologies to the amino acid sequences for antigens (a)-(h) and (1) were detected. The amino acid sequence for antigen (i) was found to be homologous to a sequence from M. leprae. The full length M. leprae sequence was amplified from genomic DNA using the sequence obtained from GENBANK. This sequence was then used to screen the M. tuberculosis library described below in Example 2 and a full length copy ofthe M. tuberculosis homologue was obtained (SEQ ID No. 99). The amino acid sequence for antigen (j) was found to be homologous to a known M. tuberculosis protein translated from a DNA sequence. To the best of the inventors' knowledge, this protein has not been previously shown to possess T-cell stimulatory activity. The amino acid sequence for antigen (k) was found to be related to a sequence from M. leprae. In the proliferation and IFN-γ assays described above, using three PPD positive donors, the results for representative antigens provided above are presented in Table 1: O 97/09428 32 TABLE 1 RESULTS OF PBMC PROLIFERATION AND IFN-Y ASSAYS In Table 1, responses that gave a stimulation index (SI) of between 2 and 4 (compared to cells cultured in medium alone) were scored as +, an SI of 4-8 or 2-4 at a concentration of 1 μg or less was scored as ++ and an SI of greater than 8 was scored as +++. The antigen of sequence (i) was found to have a high SI ( ■ +++) for one donor and lower SI (++ and +) for the two other donors in both proliferation and IFN-γ assays. These results indicate that these antigens are capable of inducing proliferation and/or interferon-γ production. EXAMPLE 2 USE OF PATIENT SERA TO ISOLATE M. TUBERCULOSIS ANTIGENS This example illustrates the isolation of antigens from M. tuberculosis lysate by screening with serum from M. tuberculosis-infected individuals. Dessicated M. tuberculosis H37Ra (Difco Laboratories) was added to a 2% NP40 solution, and alternately homogenized and sonicated three times. The resulting suspension was centrifuged at 13,000 φm in microfuge tubes and the supernatant put through a 0.2 micron syringe filter. The filtrate was bound to Macro Prep DEAE beads (BioRad, Hercules, CA). The beads were extensively washed with 20 mM Tris pH 7.5 and bound proteins eluted with IM NaCl. The IM NaCl elute was dialyzed overnight against 10 mM Tris, pH 7.5. Dialyzed solution was treated with JJ DNase and RNase at 0.05 mg/ml for 30 min. at room temperature and then with α-D- mannosidase. 0.5 U/mg at pH 4.5 for 3-4 hours at room temperature. After returning to pH 7.5, the material was fractionated via FPLC over a Bio Scale-Q-20 column (BioRad). Fractions were combined into nine pools, concentrated in a Centriprep 10 (Amicon, Beverley, MA) and then screened by Western blot for serological activity using a serum pool from M. tuberculosis-infected patients which was not immunoreactive with other antigens ofthe present invention. The most reactive fraction was run in SDS-PAGE and transferred to PNDF. A band at approximately 85 Kd was cut out yielding the sequence: (m) Xaa-Tyr-Ile-Ala-Tyr-Xaa-Thr-Thr-Ala-Gly-Ile-Val-Pro-Gly-Lys- Ile-Asn-Val-His-Leu-Val: (SEQ ID No. 137), wherein Xaa may be any amino acid. Comparison of this sequence with those in the gene bank as described above, revealed no significant homologies to known sequences. EXAMPLE 3 PREPARATION OF DNA SEQUENCES ENCODING M TUBERCULOSIS ANTIGENS This example illustrates the preparation of DNA sequences encoding M. tuberculosis antigens by screening a M. tuberculosis expression library with sera obtained from patients infected with M. tuberculosis, or with anti-sera raised against soluble M. tuberculosis antigens. A. PREPARATION OF M. TUBERCULOSIS SOLUBLE ANTIGENS USING RABBIT ANTI- SERA Genomic DNA was isolated from the M. tuberculosis strain H37Ra. The DNA was randomly sheared and used to construct an expression library using the Lambda ZAP expression system (Stratagene. La Jolla, CA). Rabbit anti-sera was generated against secretory proteins of the M. tuberculosis strains H37Ra, H37Rv and Erdman by immunizing a rabbit with concentrated supernatant of the M. tuberculosis cultures. Specifically, the rabbit was first immunized subcutaneously with 200 μg of protein antigen in a total volume of 2 ml containing 10 μg muramyl dipeptide (Calbiochem, La Jolla, CA) and 1 ml of incomplete Freund's adjuvant. Four weeks later the rabbit was boosted subcutaneously with 100 μg antigen in incomplete Freund's adjuvant. Finally, the rabbit was immumzed intravenously four weeks later with 50 μg protein antigen. The anti-sera were used to screen the expression library as described in Sambrook et al., Molecular Cloning: A Laboratory Manual, Cold Spring Harbor Laboratories, Cold Spring Harbor, NY, 1989. Bacteriophage plaques expressing immunoreactive antigens were purified. Phagemid from the plaques was rescued and the nucleotide sequences ofthe M. tuberculosis clones deduced. Thirty two clones were purified. Of these, 25 represent sequences that have not been previously identified in human M. tuberculosis. Recombinant antigens were expressed and purified antigens used in the immunological analysis described in Example 1. Proteins were induced by IPTG and purified by gel elution, as described in Skeiky et al., J. Exp. Med. 181:1527-1537, 1995. Representative sequences of DNA molecules identified in this screen are provided in SEQ ID Nos.: 1-25. The corresponding predicted amino acid sequences are shown in SEQ ID Nos. 63-87. On comparison of these sequences with known sequences in the gene bank using the databases described above, it was found that the clones referred to hereinafter as TbRA2A, TbRA16, TbRA18, and TbRA29 (SEQ ID Nos. 76, 68, 70, 75) show some homology to sequences previously identified in Mycobacterium leprae but not in M. tuberculosis. TbRAl 1, TbRA26, TbRA28 and TbDPEP (SEQ ID Nos.: 65, 73, 74, 53) have been previously identified in M. tuberculosis. No significant homologies were found to TbRAl, TbRA3, TbRA4, TbRA9, TbRAl 0, TbRAl 3, TbRAl 7, TbRal 9, TbRA29, TbRA32, TbRA36 and the overlapping clones TbRA35 and TbRAl 2 (SEQ ID Nos. 63, 77, 81, 82, 64, 67, 69, 71, 75, 78, 80, 79, 66). The clone TbRa24 is overlapping with clone TbRa29. The results of PBMC proliferation and interferon-γ assays performed on representative recombinant antigens, and using T-cell preparations from several different M. tuberculosis-immυne patients, are presented in Tables 2 and 3, respectively. TABLE 2 RESULTS OF PBMC PROLIFERATION TO REPRESENTATIVE SOLUBLE ANTIGENS nt = not tested TABLE 3 RESULTS OF PBMC iNTERFERON-γ PRODUCTION To REPRESENTATIVE SOLUBLE ANTIGENS In Tables 2 and 3, responses that gave a stimulation index (SI) of between 1.2 and 2 (compared to cells cultured in medium alone) were scored as ±, a SI of 2-4 was scored as +, as SI of 4-8 or 2-4 at a concentration of 1 μg or less was scored as ++ and an SI of greater than 8 was scored as +++. In addition, the effect of concentration on proliferation and interferon-γ production is shown for two ofthe above antigens in the attached Figure. For both proliferation and interferon-γ production, TbRa3 was scored as ++ and TbRa9 as +. These results indicate that these soluble antigens can induce proliferation and/or interferon-γ production in T-cells derived from an M. tuberculosis-immune individual. B. USE OF PATIENT SERA TO IDENTIFY DNA SEQUENCES ENCODING M. TUBERCULOSIS ANTIGENS The genomic DNA library described above, and an additional H37Rv library, were screened using pools of sera obtained from patients with active tuberculosis. To prepare the H37Rv library, M. tuberculosis strain H37Rv genomic DNA was isolated, subjected to partial Sau3A digestion and used to construct an expression library using the Lambda Zap expression system (Stratagene, La Jolla, Ca). Three different pools of sera, each containing sera obtained from three individuals with active pulmonary or pleural disease, were used in the expression screening. The pools were designated TbL, TbM and TbH, referring to relative reactivity with H37Ra lysate (i.e., TbL = low reactivity, TbM = medium reactivity and TbH = high reactivity) in both ELISA and immunoblot format. A fourth pool of sera from seven patients with active pulmonary tuberculosis was also employed. All of the sera lacked increased reactivity with the recombinant 38 kD M. tuberculosis H37Ra phosphate-binding protein. All pools were pre-adsorbed with E. coli lysate and used to screen the H37Ra and H37Rv expression libraries, as described in Sambrook et al., Molecular Cloning: A Laboratory Manual, Cold Spring Harbor Laboratories, Cold Spring Harbor, NY, 1989. Bacteriophage plaques expressing immunoreactive antigens were purified. Phagemid from the plaques was rescued and the nucleotide sequences of the M. tuberculosis clones deduced. O 97/09428 38 Thirty two clones were purified. Of these, 31 represented sequences that had not been previously identified in human M. tuberculosis. Representative sequences of the DNA molecules identified are provided in SEQ ID Nos.: 26-51 and 105. Of these, TbH-8 and TbH-8-2 (SEQ. ID NO. 105) are non-contiguous DNA sequences from the same clone, and TbH-4 (SEQ. ID NO. 43) and TbH-4-FWD (SEQ. ID NO. 44) are non-contiguous sequences from the same clone. Amino acid sequences for the antigens hereinafter identified as Tb38-1, TbH-4, TbH-8, TbH-9, and TbH- 12 are shown in SEQ ID Nos.: 88-92. Comparison of these sequences with known sequences in the gene bank using the databases identified above revealed no significant homologies to TbH-4, TbH-8, TbH-9 and TbM-3, although weak homologies were found to TbH-9. TbH- 12 was found to be homologous to a 34 kD antigenic protein previously identified in M. paratuberculosis (Ace. No. S28515). Tb38-1 was found to be located 34 base pairs upstream of the open reading frame for the antigen ESAT-6 previously identified in M. bovis (Ace. No. U34848) and in M. tuberculosis (Sorensen et al., Infec. Immun. 63: 1710- 1717, 1995). Probes derived from Tb38-1 and TbH-9, both isolated from an H37Ra library, were used to identify clones in an H37Rv library. Tb38-1 hybridized to Tb38-lF2, Tb38-lF3, Tb38-lF5 and Tb38-lF6 (SEQ. ID NOS. 112, 113, 116, 118, and 119). (SEQ ID NOS. 112 and 113 are non-contiguous sequences from clone Tb38- 1F2.) Two open reading frames were deduced in Tb38-IF2; one corresponds to Tb37FL (SEQ. ID. NO. 114), the second, a partial sequence, may be the homologue of Tb38-1 and is called Tb38-IN (SEQ. ID NO. 115). The deduced amino acid sequence of Tb38- 1F3 is presented in SEQ. ID. NO. 117. A TbH-9 probe identified three clones in the H37Rv library: TbH-9-FL (SEQ. ID NO. 106), which may be the homologue of TbH-9 (R37Ra), TbH-9-1 (SEQ. ID NO. 108), and TbH-9-4 (SEQ. ID NO. 110), all of which are highly related sequences to TbH-9. The deduced amino acid sequences for these three clones are presented in SEQ ID NOS. 107, 109 and 111. The results of T-cell assays performed on Tb38-1, ESAT-6 and other representative recombinant antigens are presented in Tables 4 A, B and 5, respectively, below: 97/09428 39 TABLE 4A RESULTS OF PBMC PROLIFERATION TO REPRESENTATIVE ANTIGENS TABLE 4B RESULTS OF PBMC iNTERFERON-γ PRODUCTION TO REPRESENTATIVE ANTIGENS 97/09428 40 TABLE 5 SUMMARY OF T-CELL RESPONSES TO REPRESENTATIVE ANTIGENS These results indicate that both the inventive M. tuberculosis antigens and ESAT-6 can induce proliferation and or interferon-γ production in T-cells derived from an M. tuberculosis-immυne individual. To the best of the inventors' knowledge, ESAT-6 has not been previously shown to stimulate human immune responses A set of six overlapping peptides covering the amino acid sequence of the antigen Tb38-1 was constructed using the method described in Example 4. The sequences of these peptides, hereinafter referred to as pep 1-6, are provided in SEQ ID Nos. 93-98, respectively. The results of T-cell assays using these peptides are shown in Tables 6 and 7. These results confirm the existence, and help to localize T-cell epitopes within Tb38-1 capable of inducing proliferation and interferon-γ production in T-cells derived from an M. tuberculosis immune individual. TABLE 6 RESULTS OF PBMC PROLIFERATION TO TB38- 1 PEPTIDES TABLE 7 RESULTS OF PBMC iNTERFERON-γ PRODUCTION TO TB38-1 PEPTIDES EXAMPLE 4 PURIFICATION AND CHARACTERIZATION OF A POLYPEPTIDE FROM TUBERCULIN PURIFIED PROTEΓN DERIVATIVE An M. tuberculosis polypeptide was isolated from tuberculin purified protein derivative (PPD) as follows. PPD was prepared as published with some modification (Seibert, F. et al., Tuberculin purified protein derivative. Preparation and analyses of a large quantity for standard. The American Review of Tuberculosis 44:9-25, 1941). M. tuberculosis Rv strain was grown for 6 weeks in synthetic medium in roller bottles at 37°C. Bottles containing the bacterial growth were then heated to 100° C in water vapor for 3 hours. Cultures were sterile filtered using a 0.22 μ filter and the liquid phase was concentrated 20 times using a 3 kD cut-off membrane. Proteins were precipitated once with 50% ammonium sulfate solution and eight times with 25% ammonium sulfate solution. The resulting proteins (PPD) were fractionated by reverse phase liquid chromatography (RP-HPLC) using a C18 column (7.8 x 300 mM; Waters, Milford, MA) in a Biocad HPLC system (Perseptive Biosystems, Framingham, MA). Fractions were eluted from the column with a linear gradient from 0-100% buffer (0.1% TFA in acetonitrile). The flow rate was 10 ml/minute and eluent was monitored at 214 nm and 280 nm. Six fractions were collected, dried, suspended in PBS and tested individually in M. tuberculosis-infected guinea pigs for induction of delayed type hypersensitivity (DTH) reaction. One fraction was found to induce a strong DTH reaction and was subsequently fractionated further by RP-HPLC on a microbore Nydac C18 column (Cat. No. 218TP5115) in a Perkin Elmer/Applied Biosystems Division Model 172 HPLC. Fractions were eluted with a linear gradient from 5-100% buffer (0.05% TFA in acetonitrile) with a flow rate of 80 μl/minute. Eluent was monitored at 215 nm. Eight fractions were collected and tested for induction of DTH in M. tuberculosis-infected guinea pigs. One fraction was found to induce strong DTH of 97/09428 44 about 16 mm induration. The other fractions did not induce detectable DTH. The positive fraction was submitted to SDS-PAGE gel electrophoresis and found to contain a single protein band of approximately 12 kD molecular weight. This polypeptide, herein after referred to as DPPD, was sequenced from the amino terminal using a Perkin Elmer/Applied Biosystems Division Procise 492 protein sequencer as described above and found to have the N-terminal sequence shown in SEQ ID No.: 129. Comparison of this sequence with known sequences in the gene bank as described above revealed no known homologies. Four cyanogen bromide fragments of DPPD were isolated and found to have the sequences shown in SEQ ID Nos.: 130-133. The ability ofthe antigen DPPD to stimulate human PBMC to proliferate and to produce IFN-γ was assayed as described in Example 1. As shown in Table 8, DPPD was found to stimulate proliferation and elicit production of large quantities of IFN-γ; more than that elicited by commercial PPD. TABLE 8 RESULTS OF PROLIFERATION AND INTERFERON-Y ASSAYS TO DPPD EXAMPLE 5 SYNTHESIS OF SYNTHETIC POLYPEPTIDES Polypeptides may be synthesized on a Millipore 9050 peptide synthesizer using FMOC chemistry with HPTU (O-Benzotriazole-N,N,N',N'- tetramethyluronium hexafluorophosphate) activation. A Gly-Cys-Gly sequence may be attached to the amino terminus of the peptide to provide a method of conjugation or labeling ofthe peptide. Cleavage ofthe peptides from the solid support may be carried out using the following cleavage mixture: trifluoroacetic acid:ethanedithiol:thioanisole:water:phenol (40: 1 :2:2:3). After cleaving for 2 hours, the peptides may be precipitated in cold methyl-t-butyl-ether. The peptide pellets may then be dissolved in water containing 0.1% trifluoroacetic acid (TFA) and lyophilized prior to purification by C18 reverse phase HPLC. A gradient of 0%-60% acetonitrile (containing 0.1% TFA) in water (containing 0.1 % TFA) may be used to elute the peptides. Following lyophilization of the pure fractions, the peptides may be characterized using electrospray mass spectrometry and by amino acid analysis. From the foregoing, it will be appreciated that, although specific embodiments ofthe invention have been described herein for the purpose of illustration, various modifications may be made without deviating from the spirit and scope of the invention. SEQUENCE LISTING (1) GENERAL INFORMATION: (i) APPLICANTS: Corixa Corporation (ii) TITLE OF INVENTION: COMPOUNDS AND METHODS FOR IMMUNOTHERAPY AND DIAGNOSIS OF TUBERCULOSIS (iii) NUMBER OF SEQUENCES: 137 (iv) CORRESPONDENCE ADDRESS: (A) ADDRESSEE: SEED and BERRY LLP (B) STREET: 6300 Columbia Center. 701 Fifth Avenue (C) CITY: Seattle (D) STATE: Washington (E) COUNTRY: USA (F) ZIP: 98104-7092 ( v ) COMPUTER READABLE FORM : (A) MEDIUM TYPE : Fl oppy di sk (B) COMPUTER: IBM PC compati bl e (C) OPERATING SYSTEM : PC-DOS/MS-DOS (D) SOFTWARE : Patentin Rel ease #1 . 0. Versi on #1 .30 (vi ) CURRENT APPLICATION DATA: (A) APPLICATION NUMBER: (B) FILING DATE: 27-AUG-1996 (C) CLASSIFICATION: (viii) ATTORNEY/AGENT INFORMATION: (A) NAME: Maki . David J. (B) REGISTRATION NUMBER: 31.392 (C) REFERENCE/DOCKET NUMBER: 210121.41IPC (ix) TELECOMMUNICATION INFORMATION: (A) TELEPHONE: (206) 622-4900 (B) TELEFAX: (206) 682-6031 (2) INFORMATION FOR SEQ ID N0:1: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 766 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID N0:1: CGAGGCACCG GTAGTTTGAA CCAAACGCAC AATCGACGGG CAAACGAACG GAAGAACACA 60 ACCATGAAGA TGGTGAAATC GATCGCCGCA GGTCTGACCG CCGCGGCTGC AATCGGCGCC 120 GCTGCGGCCG GTGTGACTTC GATCATGGCT GGCGGCCCGG TCGTATACCA GATGCAGCCG 180 GTCGTCπCG GCGCGCCACT GCCGTTGGAC CCGGCATCCG CCCCTGACGT CCCGACCGCC 240 GCCCAGTTGA CCAGCCTGCT CAACAGCCTC GCCGATCCCA ACGTGTCGTT TGCGAACAAG 300 GGCAGTCTGG TCGAGGGCGG CATCGGGGGC ACCGAGGCGC GCATCGCCGA CCACAAGCTG 360 AAGAAGGCCG CCGAGCACGG GGATCTGCCG CTGTCGTTCA GCGTGACGAA CATCCAGCCG 420 GCGGCCGCCG GTTCGGCCAC CGCCGACGTT TCCGTCTCGG GTCCGAAGCT CTCGTCGCCG 480 GTCACGCAGA ACGTCACGTT CGTGAATCAA GGCGGCTGGA TGCTGTCACG CGCATCGGCG 540 ATGGAGπGC TGCAGGCCGC AGGGNAACTG ATTGGCGGGC CGGNTTCAGC CCGCTGTTCA 600 GCTACGCCGC CCGCCTGGTG ACGCGTCCAT GTCGAACACT CGCGCGTGTA GCACGGTGCG 660 GTNTGCGCAG GGNCGCACGC ACCGCCCGGT GCAAGCCGTC CTCGAGATAG GTGGTGNCTC 720 GNCACCAGNG ANCACCCCCN NNTCGNCNNT TCTCGNTGNT GNATGA 766 (2) INFORMATION FOR SEQ ID NO:2: (A) LENGTH: 752 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (xi ) SEQUENCE DESCRIPTION : SEQ ID N0: 2: ATGCATCACC ATCACCATCA CGATGAAGTC ACGGTAGAGA CGACCTCCGT CTTCCGCGCA 60 GACπCCTCA GCGAGCTGGA CGCTCCTGCG CAAGCGGGTA CGGAGAGCGC GGTCTCCGGG 120 GTGGAAGGGC TCCCGCCGGG CTCGGCGTTG CTGGTAGTCA AACGAGGCCC CAACGCCGGG 180 TCCCGGTTCC TACTCGACCA AGCCATCACG TCGGCTGGTC GGCATCCCGA CAGCGACATA 240 TTTCTCGACG ACGTGACCGT GAGCCGTCGC CATGCTGAAT TCCGGπGGA AAACAACGAA 300 πCAATGTCG TCGATGTCGG GAGTCTCAAC GGCACCTACG TCAACCGCGA GCCCGTGGAT 360 TCGGCGGTGC TGGCGAACGG CGACGAGGTC CAGATCGGCA AGCTCCGGπ GGTGTTCTTG 420 ACCGGACCCA AGCAAGGCGA GGATGACGGG AGTACCGGGG GCCCGTGAGC GCACCCGATA 480 GCCCCGCGCT GGCCGGGATG TCGATCGGGG CGGTCCTCCG ACCTGCTACG ACCGGATTTT 540 CCCTGATGTC CACCATCTCC AAGAπCGAT TCπGGGAGG CπGAGGGTC NGGGTGACCC 600 CCCCGCGGGC CTCAπCNGG GGTNTCGGCN GGTTTCACCC CNTACCNACT GCCNCCCGGN 660 πGCNAAπC NπcπCNCT GCCCNNAAAG GGACCNπAN CπGCCGCTN GAAANGGTNA 720 TCCNGGGCCC NTCCTNGAAN CCCCNTCCCC CT 752 (2) INFORMATION FOR SEQ ID N0 : 3 : (i ) SEQUENCE CHARACTERISTICS : (A) LENGTH : 813 base pai rs (B) TYPE : nucl ei c aci d (C) STRANDEDNESS : si ngl e (D) TOPOLOGY : l i near „ ,„„,„„ PCT/US96/14674 WO 97/09428 49 (xi ) SEQUENCE DESCRIPTION : SEQ ID N0: 3 : CATATGCATC ACCATCACCA TCACACπCT AACCGCCCAG CGCGTCGGGG GCGTCGAGCA 60 CCACGCGACA CCGGGCCCGA TCGATCTGCT AGCπGAGTC TGGTCAGGCA TCGTCGTCAG 120 CAGCGCGATG CCCTATGTπ GTCGTCGACT CAGATATCGC GGCAATCCAA TCTCCCGCCT 180 GCGGCCGGCG GTGCTGCAAA CTACTCCCGG AGGAA TTCG ACGTGCGCAT CAAGATCπC 240 ATGCTGGTCA CGGCTGTCGT 7TTGCTCTGT TGπCGGGTG TGGCCACGGC CGCGCCCAAG 300 ACCTACTGCG AGGAGπGAA AGGCACCGAT ACCGGCCAGG CGTGCCAGAT TCAAATGTCC 360 GACCCGGCCT ACAACATCAA CATCAGCCTG CCCAGπACT ACCCCGACCA GAAGTCGCTG 420 GAAAAπACA TCGCCCAGAC GCGCGACAAG πCCTCAGCG CGGCCACATC GTCCACTCCA 480 CGCGAAGCCC CCTACGAAπ GAATATCACC TCGGCCACAT ACCAGTCCGC GATACCGCCG 540 CGTGGTACGC AGGCCGTGGT GCTCAMGGTC TACCACAACG CCGGCGGCAC GCACCCAACG 600 ACCACGTACA AGGCCπCGA πGGGACCAG GCCTATCGCA AGCCAATCAC CTATGACACG 660 CTGTGGCAGG CTGACACCGA TCCGCTGCCA GTCGTCπCC CCAπGπGC AAGGTGAACT 720 GAGCAACGCA GACCGGGACA ACWGGTATCG ATAGCCGCCN AATGCCGGCT TGGAACCCNG 780 TGAAAπATC ACAACπCGC AGTCACNAAA NAA 813 (2) INFORMATION FOR SEQ ID N0: 4: ( i ) SEQUENCE CHARACTERISTICS : (A) LENGTH : 447 base pai rs (B) TYPE : nucl ei c aci d (C) STRANDEDNESS : si ngle (D) TOPOLOGY : l i near (xi ) SEQUENCE DESCRIPTION : SEQ ID N0:4: CGGTATGAAC ACGGCCGCGT CCGATAACπ CCAGCTGTCC CAGGGTGGGC AGGGAπCGC 60 CAπCCGATC GGGCAGGCGA TGGCGATCGC GGGCCAGATC CGATCGGGTG GGGGGTCACC 120 CACCGπCAT ATCGGGCCTA CCGCCπCCT CGGCπGGGT GπGTCGACA ACAACGGCAA 180 CGGCGCACGA GTCCAACGCG TGGTCGGGAG CGCTCCGGCG GCAAGTCTCG GCATCTCCAC 240 CGGCGACGTG ATCACCGCGG TCGACGGCGC TCCGATCAAC TCGGCCACCG CGATGGCGGA 300 CGCGCπAAC GGGCATCATC CCGGTGACGT CATCTCGGTG AACTGGCAAA CCAAGTCGGG 360 CGGCACGCGT ACAGGGAACG TGACAπGGC CGAGGGACCC CCGGCCTGAT πCGTCGYGG 420 ATACCACCCG CCGGCCGGCC AAπGGA 447 (2) INFORMATION FOR SEQ ID NO: 5 : ( i ) SEQUENCE CHARACTERISTICS : (A) LENGTH : 604 base pai rs (B) TYPE: nuclei c acid (C) STRANDEDNESS : si ngle (D) TOPOLOGY : l i near (xi ) SEQUENCE DESCRIPTION : SEQ ID N0: 5 : GTCCCACTGC GGTCGCCGAG TATGTCGCCC AGCAAATGTC TGGCAGCCGC CCAACGGAAT 60 CCGGTGATCC GACGTCGCAG GπGTCGAAC CCGCCGCCGC GGAAGTATCG GTCCATGCCT 120 AGCCCGGCGA CGGCGAGCGC CGGAATGGCG CGAGTGAGGA GGCGGGCAAT πGGCGGGGC 180 CCGGCGACGG NGAGCGCCGG AATGGCGCGA GTGAGGAGGT GGNCAGTCAT GCCCAGNGTG 240 ATCCAATCAA CCTGNAπCG GNCTGNGGGN CCATπGACA ATCGAGGTAG TGAGCGCAAA 300 TGAATGATGG AAAACGGGNG GNGACGTCCG NTGπCTGGT GGTGNTAGGT GNCTGNCTGG 360 NGTNGNGGNT ATCAGGATGT TCπCGNCGA AANCTGATGN CGAGGAACAG GGTGTNCCCG 420 NNANNCCNAN GGNGTCCNAN CCCNNNNTCC TCGNCGANAT CANANAGNCG NπGATGNGA 480 NAAAAGGGTG GANCAGNNNN AANTNGNGGN CCNAANAANC NNNANNGNNG NNAGNTNGNT 540 NNNTNπNNC ANNNNNNNTG NNGNNGNNCN NNNCAANCNN NTNNNNGNAA NNGGNπNπ 600 NAAT 604 (2) INFORMATION FOR SEQ ID NO : 6 : (i ) SEQUENCE CHARACTERISTICS : (A) LENGTH: 633 base pai rs (B) TYPE : nucl ei c aci d (C) STRANDEDNESS : si ngl e (D) TOPOLOGY : l i near (xi ) SEQUENCE DESCRIPTION : SEQ ID NO : 6 : πGCANGTCG AACCACCTCA CTAAAGGGAA CAAAAGCTNG AGCTCCACCG CGGTGGCGGC 60 CGCTCTAGAA CTAGTGKATM YYYCKGGCTG CAGSAATYCG GYACGAGCAT TAGGACAGTC 120 TAACGGTCCT GπACGGTGA TCGAATGACC GACGACATCC TGCTGATCGA CACCGACGAA 180 CGGGTGCGAA CCCTCACCCT CAACCGGCCG CAGTCCCGYA ACGCGCTCTC GGCGGCGCTA 240 CGGGATCGGT πTTCGCGGY GπGGYCGAC GCCGAGGYCG ACGACGACAT CGACGTCGTC 300 ATCCTCACCG GYGCCGATCC GGTGπCTGC GCCGGACTGG ACCTCAAGGT AGCTGGCCGG 360 GCAGACCGCG CTGCCGGACA TCTCACCGCG GTGGGCGGCC ATGACCAAGC CGGTGATCGG 420 CGCGATCAAC GGCGCCGCGG TCACCGGCGG GCTCGAACTG GCGCTGTACT GCGACATCCT 480 GATCGCCTCC GAGCACGCCC GCπCGNCGA CACCCACGCC CGGGTGGGGC TGCTGCCCAC 540 CTGGGGACTC AGTGTGTGCT TGCCGCAAAA GGTCGGCATC GGNCTGGGCC GGTGGATGAG 600 CCTGACCGGC GACTACCTGT CCGTGACCGA CGC 633 (2) INFORMATION FOR SEQ ID NO: 7 : ( i ) SEQUENCE CHARACTERISTICS : (A) LENGTH : 1362 base pai rs (B) TYPE: nucleic aci d (C) STRANDEDNESS : si ngle (D) TOPOLOGY: l i near (xi) SEQUENCE DESCRIPTION: SEQ ID N0:7: CGACGACGAC GGCGCCGGAG AGCGGGCGCG AACGGCGATC GACGCGGCCC TGGCCAGAGT 60 CGGCACCACC CAGGAGGGAG TCGAATCATG AAATπGTCA ACCATAπGA GCCCGTCGCG 120 CCCCGCCGAG CCGGCGGCGC GGTCGCCGAG GTCTATGCCG AGGCCCGCCG CGAGπCGGC 180 CGGCTGCCCG AGCCGCTCGC CATGCTGTCC CCGGACGAGG GACTGCTCAC CGCCGGCTGG 240 GCGACGπGC GCGAGACACT GCTGGTGGGC CAGGTGCCGC GTGGCCGCAA GGAAGCCGTC 300 GCCGCCGCCG TCGCGGCCAG CCTGCGCTGC CCCTGGTGCG TCGACGCACA CACCACCATG 360 CTGTACGCGG CAGGCCAAAC CGACACCGCC GCGGCGATCT TGGCCGGCAC AGCACCTGCC 420 GCCGGTGACC CGAACGCGCC GTATGTGGCG TGGGCGGCAG GAACCGGGAC ACCGGCGGGA 480 CCGCCGGCAC CGπCGGCCC GGATGTCGCC GCCGAATACC TGGGCACCGC GGTGCAAπC 540 CACπCATCG CACGCCTGGT CCTGGTGCTG CTGGACGAAA CCπCCTGCC GGGGGGCCCG 600 CGCGCCCAAC AGCTCATGCG CCGCGCCGGT GGACTGGTGT TCGCCCGCAA GGTGCGCGCG 660 GAGCATCGGC CGGGCCGCTC CACCCGCCGG CTCGAGCCGC GAACGCTGCC CGACGATCTG 720 GCATGGGCAA CACCGTCCGA GCCCATAGCA ACCGCGπCG CCGCGCTCAG CCACCACCTG 780 GACACCGCGC CGCACCTGCC GCCACCGACT CGTCAGGTGG TCAGGCGGGT CGTGGGGTCG 840 TGGCACGGCG AGCCAATGCC GATGAGCAGT CGCTGGACGA ACGAGCACAC CGCCGAGCTG 900 CCCGCCGACC TGCACGCGCC CACCCGTCTT GCCCTGCTGA CCGGCCTGGC CCCGCATCAG 960 GTGACCGACG ACGACGTCGC CGCGGCCCGA TCCCTGCTCG ACACCGATGC GGCGCTGGπ 1020 GGCGCCCTGG CCTGGGCCGC CπCACCGCC GCGCGGCGCA TCGGCACCTG GATCGGCGCC 1080 GCCGCCGAGG GCCAGGTGTC GCGGCAAAAC CCGACTGGGT GAGTGTGCGC GCGCTGTCGG 1140 TAGGGTGTCA TCGCTGGCCC GAGGGATCTC GCGGCGGCGA ACGGAGGTGG CGACACAGGT 1200 GGAAGCTGCG CCCACTGGCT TGCGCCCCAA CGCCGTCGTG GGCGπCGGT TGGCCGCACT 1260 GGCCGATCAG GTCGGCGCCG GCCCπGGCC GAAGGTCCAG CTCAACGTGC CGTCACCGAA 1320 GGACCGGACG GTCACCGGGG GTCACCCTGC GCGCCCAAGG AA 1362 (2) INFORMATION FOR SEQ ID NO:8: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 1458 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear ( xi ) SEQUENCE DESCRIPTION : SEQ ID NO : 8 : GCGACGACCC CGATATGCCG GGCACCGTAG CGAAAGCCGT CGCCGACGCA CTCGGGCGCG 60 GTATCGCTCC CGπGAGGAC AπCAGGACT GCGTGGAGGC CCGGCTGGGG GAAGCCGGTC 120 TGGATGACGT GGCCCGTGπ TACATCATCT ACCGGCAGCG GCGCGCCGAG CTGCGGACGG 180 CTAAGGCCπ GCTCGGCGTG CGGGACGAGT TAAAGCTGAG CπGGCGGCC GTGACGGTAC 240 TGCGCGAGCG CTATCTGCTG CACGACGAGC AGGGCCGGCC GGCCGAGTCG ACCGGCGAGC 300 TGATGGACCG ATCGGCGCGC TGTGTCGCGG CGGCCGAGGA CCAGTATGAG CCGGGCTCGT 360 CGAGGCGGTG GGCCGAGCGG πCGCCACGC TAπACGCAA CCTGGAAπC CTGCCGAAπ 420 CGCCCACGπ GATGAACTCT GGCACCGACC TGGGACTGCT CGCCGGCTGT πTGπCTGC 480 JPΘU L L :λ90 ~ !0d01 (0) 3 | 6U LS : sS N03αNVyiS (3) ppe DLθLonu :3dλl (8) s LBd θseq 298 :H19N31 (V) : S3LL$Ic'313VrJVH3 33N3003S ( .«- ) : 6 -0N 01 03S OJ NOIlVWyOJ I (2) 8SfrI V39993V9 3313931933 GW 133V3199V3 V393W3939 9V93339993 1993939311 99339V1V93 3V3LL93993 08CT 3311V39399 9939V9W93 3991399V99 3931V3993V 3V39399399 V39V3V1V39 02εi 319391V313 99333V339V 1199391933 9W9W919V 3V93V19331 1V199913V3 0921 9339113913 W99399111 9991V319V9 991399931V 9W39333V3 3939333993 0021 99V9199913 W93333113 333V139339 V3191V931V 3193V91V91 1331199391 OH I 9939919199 3393199V99 V93139933V 99913V9319 3931993V93 3931391V99 080 T 33393133W 31V9313993 131W191V3 19V93V1133 913913V333 199V999939 0201 19333W33V 9399V931V3 93399V9V99 9933919933 3VW3999V1 W31V93V3V 096 9313111919 9139993331 V939919933 93V3939339 VW39131V3 393V931191 006 39V9339339 33391V9939 3931931V9V V39933W93 9331W3199 139933V3V1 0178 33993W393 W93193399 9391331193 93V933V919 199119931V 133W3111V 08Z 39333139V9 39V333331V V93399W33 933V319311 1V919131V1 V99333V393 02Z 19191V9JLL3 91913991V1 9133939919 3993393199 39991V3313 1991919993 099 933919V3V9 1V1913993V 1311193191 9933V9939V 33993V3993 9993V33133 009 99199931V9 999339333V 939133V339 V3119391V1 V9933V3993 99V9913999 O S 39V39139V9 3393399V3V 9991393V93 9ilI31V931 W3913931L V99V911V93 K9H/96Sn/XDJ 8W60/I6 OΛV (xi ) SEQUENCE DESCRIPTION : SEQ ID N0: 9 : ACGGTGTAAT CGTGCTGGAT CTGGAACCGC GTGGCCCGCT ACCTACCGAG ATCTACTGGC 60 GGCGCAGGGG GCTGGCCCTG GGCATCGCGG TCGTCGTAGT CGGGATCGCG GTGGCCATCG 120 TCATCGCCπ CGTCGACAGC AGCGCCGGTG CCAAACCGGT CAGCGCCGAC AAGCCGGCCT 180 CCGCCCAGAG CCATCCGGGC TCGCCGGCAC CCCAAGCACC CCAGCCGGCC GGGCAAACCG 240 AAGGTAACGC CGCCGCGGCC CCGCCGCAGG GCCAAAACCC CGAGACACCC ACGCCCACCG 300 CCGCGGTGCA GCCGCCGCCG GTGCTCAAGG AAGGGGACGA πGCCCCGAT TCGACGCTGG 360 CCGTCAAAGG πTGACCAAC GCGCCGCAGT ACTACGTCGG CGACCAGCCG AAGπCACCA 420 TGGTGGTCAC CAACATCGGC CTGGTGTCCT GTAAACGCGA CGπGGGGCC GCGGTGπGG 480 CCGCCTACGT πACTCGCTG GACAACAAGC GGπGTGGTC CAACCTGGAC TGCGCGCCCT 540 CGAATGAGAC GCTGGTCAAG ACGTπTCCC CCGGTGAGCA GGTAACGACC GCGGTGACCT 600 GGACCGGGAT GGGATCGGCG CCGCGCTGCC CAπGCCGCG GCCGGCGATC GGGCCGGGCA 660 CCTACAATCT CGTGGTACAA CTGGGCAATC TGCGCTCGCT GCCGGπCCG πCATCCTGA 720 ATCAGCCGCC GCCGCCGCCC GGGCCGGTAC CCGCTCCGGG TCCAGCGCAG GCGCCTCCGC 780 CGGAGTCTCC CGCGCAAGGC GGATAAπAT TGATCGCTGA TGGTCGAπC CGCCAGCTGT 840 GACAACCCCT CGCCTCGTGC CG 862 (2 ) INFORMATION FOR SEQ ID NO : 10 : ( T ) SEQUENCE CHARACTERISTICS : (A) LENGTH : 622 base pai rs (B) TYPE : nucl ei c aci d (C) STRANDEDNESS : si ngle (D) TOPOLOGY : l i near 081 1V13193119 V39V991V3391WW9W3 V3933V93139939V3313V 33139V99W 021 9W3993993913V391993199913193V V99399V39399V3193193139V3W33V 09 399199399391V39V3V911919913V3V 39933933991191339W19939V39399 ■ II-ON QI 03S : N0IldIc!0S3Q 33N3003S (PO JPΘULL :λ9010d01 (0) ΘLSULS :sS3Nα3QNVaiS (3) P B op nu :3dλl (8) SJLBd θS q 002T :H19N3T (V) • SOIlSrølDVαVHD 33N3flθ3S U) : IΪ-0N 01 D3S HOJ NOUVWaOJNI (2) 229 1311V3V9N9333V339W993 009 333V3191V939313N93V919N9933V9993993199319199199133 V991999939 Ot>S 931V919939 V3V3W9139391VW9331 V9V93199V93V933993191993991991 0817 93993V93191191119993399V933V3139139V933V 31911393399939V3V33V 02t7 9W91V93993V393993V3931V93V9119319319319113V3999339911991991 09C 19V99391939V3W991V333V3991993 V1V1V993139VW311919 V393933931 008 99W91V919 V39V99399V V39931333V 319W3919V 3V39339V199399931333 0172 1V99V311133W1393991993V339399933939VW331993919339339119911 081 9393V993939V3W31V9333933V93V93199W33V3191193193999W933919 021 V991393W939339139199199339919 V19W931931V9W33939993333V3V9 09 VW3V91W33V9199V39191999133313391V3V319099W39933 V39V31V911 • 01-ON 01 D3S -NOIldldOSSα 33N3H03S (PO 9ζ PL9Pl/96SLVlDd SZP60/L6 OΛV JP9ULL :ADOlOdOl (0) θ L β up : SS3N03αNVyiS (3) ppB αppnu :3dλl (a) s LBd θS q ggπ :H19N31 (V) : S3IlSiy313VdVH333N3HQ3S U) • 21-ON QI D3S dOJ NOUVWyOJNI (2) 0021 9V939991V999399V9339991391399391LV139V31 V19339991L 1W3931999 OHI V199V39331193391V939 V91993V9311W999W919V133V9113111V1391W 0801 91993933993991LWW39W331L931 VW33391L93311V3313993V1W33V9 0201 913399W9V V3399V331991LV939339 W391V1LL93999W1993913V19933V 096 93V9391V99333V1VW93139131931V 9V91V133V93991391931 V9333V1131 006 3991339V333V333V9V3V 131193193193V3V991LV 199133V93V V399W3V99 0178 91V31V9W33999933931 W3V9W1993199319V933V33V31V939919V331V9 08Z 93319993993193V31V31 V9V333991V 3W9U.9V39 W199919939111931991 02Z 9V93W3V133V31V9319993V933V93V 9V3913V1333993193W993W3W999 099 39V33939931939931939999939V31L 93VW939V339399VW399991939999 009 3W331V191993V93133V 1WV9V331L 3W3V993193V1993319V V3V939V393 Ot9 31L31V1L939V1LV933V3 W339339133V933V3993313W313339W331V9V3 0817 V331V91W99191933V31 V33V3993W 31L11V9W33933V13V333V993V9113 0217 1W91393V39V9193999V V31V1W3V133V31V93931V93339931191993V933 098 9133V9991V 399333311993919939V99399319933 V9133W319933V931933 008 1W91L9333191V993139933931LLV933VW93W3 W3131119V 333V919999 0172 3391993319993W3393V V3V13V991L 93V3V1399933391931V939193V1339 LS PL9PV96SπJlDΛ KWW6 0M : CI : ON OI D3S dOd NOIlVWbOdNI (2) SSII V3193 1339V19V93 OH I 19333V1919 39V33191LL 9V933V9993 1W3939931 393V31L9V9 1333933111 080T 11V9399311 W99939999 131V391939 V9D3919V91 3V39399399 393V999139 020T V3933993V1 3999199319 199V991393 33193V9313 9333V11393 9939991V9V 096 V3V9393919 9133399V93 199939V939 3W9199333 33931VW93 119139139V 006 93V93V3319 9V39139139 1V39393193 99139V3V39 9V93W3139 399W3V931 0t78 99V331V91V 3399199W3 1V31V3V933 993939V399 9V331V9339 393W91393 08Z 99399939V9 3393399V99 93919W319 33W39V39V 3V99139V93 339133V139 02Z 3393193399 91391993V9 3133V3V139 93V99W393 3399939V93 19V1933939 099 39133V13V9 3939199993 99311V9333 93111V1939 3V991V9V39 V93W339W 009 99V933V331 31WW91L9 V39V393191 33993V1339 39V91L9993 V1L1991399 OfrS 93V133191V 9399W3199 9339399391 19V939933V 3199V93V93 1V33391919 0817 9311919993 3319393193 1L931LV191 33V99V9999 33V3W31L9 399V931V31 0217 33999V93V9 9993319133 V399991V31 V99391V9V9 31V9V339V3 V13V933993 098 V91V91L9V9 3393V11993 V999931991 931L9393V9 99331V9939 933999393V 008 933V39331V 93331V3W9 V39133W33 3W933V931 3313139933 9933V93933 017 931V93V9V3 3W31L93V3 3V3V331V39 33993V9339 339919939V V331391L99 081 93V931933V 3199W3139 9333V3193V 93933V3339 3139131V3V V391311L93 02T 31V399933V 9W3V931L9 119319V391 39393V9339 1V993V33V3 V139933V9V 09 V33V393VW 33V9W9339 1V399913W 93V931L913 9193199V3 ) 139V39W39 : 2ϊ -0N QI 03S • NOIldI , DS3α 33N30D3S ( O 85 SZP60/L6 OΛV frZ,9H/96SΩΛL3«I 096 W33933993 993931V919 3V33W3W3 3V91L31V91 39999V9339 1319131LV3 006 1V39933139 99V99V9931 9V33933999 131V933VW 991L91V319 31919V3339 0P8 199199W33 99399199V3 W93199319 9993393391 V3VW39V39 33331V39W 08Z 3393993939 V339139919 V333993993 9V33339933 9333V39993 3W3119993 02Z 19913331V3 9339939399 39931V3993 3933191991 9939V1V93V 9199393993 099 1V33991191 V399V39193 133393W33 931L991V99 9133133333 93V91V33V9 009 3311V91939 9133V1V913 1999339933 3V19919991 19399V93V1 333W31933 Ot/9 V19V333W3 39V3933333 933331933V 333V119399 13V931L9V3 9V339V3V19 0817 3WV39V39V 39999V3139 1V1199V333 3W999339V 39V3933933 V33931LV19 02 > 93V333V31V V93V91V3V9 39V133W39 V9W99V3V1 9V13399919 V19V933399 098 1L9W33991 V393V3319V 3391V333V3 V339WV91L 913V1L9V39 191L9V133V 008 V3939393V3 319V3131W 9919V3131V 1L93W9399 3119999313 13W9V931V Ot2 3V993V39V9 9313939913 993V939199 3331L39V39 331LV93391 V993193399 08T 3333139139 193V111V93 193W99133 3339V33993 99V333V933 V3V9W931V 021 393913911V 993993V33V V313919919 9V3VW3193 1V93991L99 9313399931 09 1999339119 39993V3993 1V39931993 3V1111993V V9J 91991 31933939V9 : CI : ON QI 03S : N0Ildla3S30 33N3H03S ( LX) JBΘU L L :λ9010d01 (0) 9-6U S : SS 3Nα3αNVJlS (3) ppB oppnu :3 Al 03) SJLBd asεq \ LL \ :H19N31 (V) : S3IlSIti313VaVH3 33N3D03S ( !■) 65 %ZpmiL6 OΛV PL9Pl/96S[VlDd GCCTCCCCTG GGCAGTCCGC CGCCGAAAAC GACGGTAACC πCTCTGACG GGCGGACCGC 1020 ACCCπCACG GTGGTGGGGG CTGACCCCAC CAGTGATATC GCCGTCGTCC GTGπCAGGG 1080 CGTCTCCGGG CTCACCCCGA TCTCCCTGGG πCCTCCTCG GACCTGAGGG TCGGTCAGCC 1140 GGTGCTGGCG ATCGGGTCGC CGCTCGGTπ GGAGGGCACC GTGACCACGG GGATCGTCAG 1200 CGCTCTCAAC CGTCCAGTGT CGACGACCGG CGAGGCCGGC AACCAGAACA CCGTGCTGGA 1260 CGCCAπCAG ACCGACGCCG CGATCAACCC CGGTAACTCC GGGGGCGCGC TGGTGAACAT 1320 GAACGCTCAA CTCGTCGGAG TCAACTCGGC CAπGCCACG CTGGGCGCGG ACTCAGCCGA 1380 TGCGCAGAGC GGCTCGATCG GTCTCGGTπ TGCGAπCCA GTCGACCAGG CCAAGCGCAT 1440 CGCCGACGAG πGATCAGCA CCGGCAAGGC GTCACATGCC TCCCTGGGTG TGCAGGTGAC 1500 CAATGACAAA GACACCCCGG GCGCCAAGAT CGTCGAAGTA GTGGCCGGTG GTGCTGCCGC 1560 GAACGCTGGA GTGCCGAAGG GCGTCGπGT CACCAAGGTC GACGACCGCC CGATCAACAG 1620 CGCGGACGCG πGGπGCCG CCGTGCGGTC CAAAGCGCCG GGCGCCACGG TGGCGCTAAC 1680 CTπCAGGAT CCCTCGGGCG GTAGCCGCAC AGTGCAAGTC ACCCTCGGCA AGGCGGAGCA 1740 GTGATGAAGG TCGCCGCGCA GTGπCAAAG C 1771 (2) INFORMATION FOR SEQ ID NO : 14 : ( i ) SEQUENCE CHARACTERISTICS : (A) LENGTH : 1058 base pai rs (B) TYPE : nucl ei c aci d (C) STRANDEDNESS : si ngl e (D) TOPOLOGY : l i near (xi ) SEQUENCE DESCRIPTION : SEQ ID NO: 14 : CTCCACCGCG GTGGCGGCCG CTCTAGAACT AGTGGATCCC CCGGGCTGCA GGAAπCGGC 60 ACGAGGATCC GACGTCGCAG GπGTCGAAC CCGCCGCCGC GGAAGTATCG GTCCATGCCT 120 AGCCCGGCGA CGGCGAGCGC CGGAATGGCG CGAGTGAGGA GGCGGGCAAT πGGCGGGGC 180 CCGGCGACGG CGAGCGCCGG AATGGCGCGA GTGAGGAGGC GGGCAGTCAT GCCCAGCGTG 240 ATCCAATCAA CCTGCAπCG GCCTGCGGGC CCATπGACA ATCGAGGTAG TGAGCGCAAA 300 TGAATGATGG AAAACGGGCG GTGACGTCCG CTGπCTGGT GGTGCTAGGT GCCTGCCTGG 360 CGπGTGGCT ATCAGGATGT TCπCGCCGA AACCTGATGC CGAGGAACAG GGTGπCCCG 420 TGAGCCCGAC GGCGTCCGAC CCCGCGCTCC TCGCCGAGAT CAGGCAGTCG CπGATGCGA 480 CAAAAGGGπ GACCAGCGTG CACGTAGCGG TCCGAACAAC CGGGAAAGTC GACAGCπGC 540 TGGGTAπAC CAGTGCCGAT GTCGACGTCC GGGCCAATCC GCTCGCGGCA AAGGGCGTAT 600 GCACCTACAA CGACGAGCAG GGTGTCCCGT πCGGGTACA AGGCGACAAC ATCTCGGTGA 660 AACTGπCGA CGACTGGAGC AATCTCGGCT CGATTTCTGA ACTGTCAACT TCACGCGTGC 720 TCGATCCTGC CGCTGGGGTG ACGCAGCTGC TGTCCGGTGT CACGAACCTC CAAGCGCAAG 780 GTACCGAAGT GATAGACGGA ATπCGACCA CCAAAATCAC CGGGACCATC CCCGCGAGCT 840 CTGTCAAGAT GCπGATCCT GGCGCCAAGA GTGCAAGGCC GGCGACCGTG TGGAπGCCC 900 AGGACGGCTC GCACCACCTC GTCCGAGCGA GCATCGACCT CGGATCCGGG TCGAπCAGC 960 TCACGCAGTC GAAATGGAAC GAACCCGTCA ACGTCGACTA GGCCGAAGπ GCGTCGACGC 1020 GπGNTCGAA ACGCCCTTGT GAACGGTGTC AACGGNAC 1058 (2) INFORMATION FOR SEQ ID NO: 15 : ( i ) SEQUENCE CHARACTERISTICS : (A) LENGTH : 542 base pai rs (B) TYPE : nucl ei c aci d (C) STRANDEDNESS : si ngl e (D) TOPOLOGY : l i near 008 91LW33933 9399339333 3933393311 1133933911 933V399339 3393339W3 0fr2 3933933W9 1W93399V9 9993399V31 1193391393 3933931933 V339319339 08T 33V1L933V3 9999933933 33V39V3V1V 3391LV3393 3939933933 991333V91L 021 3933V3391V 9339339999 3393991993 3933V39933 9339111339 33V31V33V3 09 3931V39391 39V31V9339 3193393391 1V33333911 9331339393 3393391993 : 9I : ON QI D3S - NOIldrøSBQ 33N3D03S ( PO J BΘU L L : A9010d01 (0) Θ LBU L S : SS N03α VyiS (3) ppB o nu :3 λl (8) s j LBd θsεq CI6 : H19N31 (V) : S3IlSiy313VyVH333N3D03S U) : 9T : ON 0103S bOd NOIlVWdOdNI (2) 2179 99 01 9 39V939V339 93919V3133 3939133913 139933V913 9199399399 V19331939V 0817 V99V199339 9V33913919 3VW99V933 391L9V9333 91V9319333 9V33991933 OZt V91V931V91 39V9N99339 331V939991 3W9333V93 19393H391 W1L9V9933 098 93V3399399 3311V93931 V3919399V3 31V1933913 9193933199 V333993939 008 9V33V13399 V933931391 319191111V 9391931LV9 1199391119 93V3931VW 0 > 2 V393V9W39 V939933999 3V39V13939 33W393993 399V91V9W 311931919V 08T V93139W31 V3933V133V 31V9W3993 3939V3V991 933991V3V9 9V39V9 V3 02T 1999313931 939331V3V9 1V931939V1 V999393999 39V3319939 9V99399399 09 399V3W999 1331V0V333 39V33V9993 1V31V3V931 V9199V9V93 V39931LW9 ■ SI - ON 01 03S - NOIldldOSdα 33N3HD3S ( LX ) Z9 PL9Pl/96S(V±Dd ZZP60/L6 OΛV 0172 V931333391 3939333311 3V933931L9 933V99V393 1911339933 9333399399 08T V333993393 993V339913 3999139993 1933913991 391939V913 91L991V319 02T 9199V313V3 1393393393 931LW39V9 1V9993V1L9 9V99V3V3V9 3333V139V1 09 V913U1W3 V9991399W 1L333V9933 393391331V WW9V1919 91L93V13V9 • ZI - ON QI 03S : N0IldIU3S3α 33N3D03S ( PO JBΘU L L : A9010d01 (0) d[δ ιs : sS3N03αNVyiS (3) ppB oppnu : dλl (9) s j LBd asεq 2 8T : H19N31 (V) : S3USiy313VyVH3 33N3H03S Q ) : ZT ' ON 01 03S HOd NOIlVWdOdNI (2) 816 393 3993993393 006 3939933933 991LN99339 33V3393393 3311933933 91LV339339 J193393391 0178 1V3393391L V3393391L9 3393991993 33333V339V 3V193391L9 3393333993 08Z 3933991N33 9399199399 331L99S393 3119933939 V1L9339W9 1391391991 02Z 1V33933933 9199339339 1193333331 V933933319 933V333V99 3393333993 099 3V3391L999 93339WW3 3393W3393 3939933933 391939N9V9 9339399933 009 911V133339 93939V3393 3V199333W 91V1LL91W 1L933933V3 9V33933V31 OW 1V339933V3 1V3393391L 1933933339 9339339199 3W3339V3V V3VW933V3 0817 9993393391 1V33V33999 9339333V9V 33933V3999 399311V1W 3393391119 0217 3393393993 3V1L933933 3391993119 3331193393 3V11V33933 3V99339339 098 3393999339 1393993W1 1933933933 339V339339 11933V39WV 339V3W933 Z9 PL9PV96S β /lDd 8ZW0/ .6 OΛV 64 CCCGTCCGCG ATGGTCGCCC AAGTGGCGCC ACAGGTGGTC AACATCAACA CCAAACTGGG 300 CTACAACAAC GCCGTGGGCG CCGGGACCGG CATCGTCATC GATCCCAACG GTGTCGTGCT 360 GACCAACAAC CACGTGATCG CGGGCGCCAC CGACATCAAT GCGπCAGCG TCGGCTCCGG 420 CCAAACCTAC GGCGTCGATG TGGTCGGGTA TGACCGCACC CAGGATGTCG CGGTGCTGCA 480 GCTGCGCGGT GCCGGTGGCC TGCCGTCGGC GGCGATCGGT GGCGGCGTCG CGGπGGTGA 540 GCCCGTCGTC GCGATGGGCA ACAGCGGTGG GCAGGGCGGA ACGCCCCGTG CGGTGCCTGG 600 CAGGGTGGTC GCGCTCGGCC AAACCGTGCA GGCGTCGGAT TCGCTGACCG GTGCCGAAGA 660 GACAπGAAC GGGπGATCC AGπCGATGC CGCAATCCAG CCCGGTGAπ CGGGCGGGCC 720 CGTCGTCAAC GGCCTAGGAC AGGTGGTCGG TATGAACACG GCCGCGTCCG ATAACπCCA 780 GCTGTCCCAG GGTGGGCAGG GAπCGCCAT TCCGATCGGG CAGGCGATGG CGATCGCGGG 840 CCAAATCCGA TCGGGTGGGG GGTCACCCAC CGπCATATC GGGCCTACCG CCπCCTCGG 900 CπGGGTGπ GTCGACAACA ACGGCAACGG CGCACGAGTC CAACGCGTGG TCGGAAGCGC 960 TCCGGCGGCA AGTCTCGGCA TCTCCACCGG CGACGTGATC ACCGCGGTCG ACGGCGCTCC 1020 GATCAACTCG GCCACCGCGA TGGCGGACGC GCπAACGGG CATCATCCCG GTGACGTCAT 1080 CTCGGTGAAC TGGCAAACCA AGTCGGGCGG CACGCGTACA GGGAACGTGA CAπGGCCGA 1140 GGGACCCCCG GCCTGATTTG TCGCGGATAC CACCCGCCGG CCGGCCAAπ GGAπGGCGC 1200 CAGCCGTGAT TGCCGCGTGA GCCCCCGAGT TCCGTCTCCC GTGCGCGTGG CAπGTGGAA 1260 GCAATGAACG AGGCAGAACA CAGCGπGAG CACCCTCCCG TGCAGGGCAG πACGTCGAA 1320 GGCGGTGTGG TCGAGCATCC GGATGCCAAG GACπCGGCA GCGCCGCCGC CCTGCCCGCC 1380 GATCCGACCT GGTπAAGCA CGCCGTCπC TACGAGGTGC TGGTCCGGGC GπcπCGAC 1440 GCCAGCGCGG ACGGπCCGN CGATCTGCGT GGACTCATCG ATCGCCTCGA CTACCTGCAG 1500 TGGCπGGCA TCGACTGCAT CTGπGCCGC CGπCCTACG ACTCACCGCT GCGCGACGGC 1560 GGπACGACA πCGCGACπ CTACAAGGTG CTGCCCGAAT TCGGCACCGT CGACGATTTC 1620 009 93W991VW 9319V393V3 139V311V93 1999331V99 3133V931V3 9V939V9331 01 9 93133V33V3 9313993V99 V33391LV99 191933V939 93399W391 9V9W33939 0817 91331V91L3 91V9W3191 3139V93933 331V33V999 33V31VVW3 3V33V931LL 0217 W993V9V1V 919W933V1 99W3939W 33133W93V 3191993319 139139V393 098 V919999139 3391331V93 13919393V3 1L3W31913 W9131UV9 313993131V 008 V39V9913V9 3V931L913V W91993131 V3W3V9399 W3V199931 1193331919 0 >2 99V39V93V9 3W3V133V3 91V193999V W39939313 9331W3399 933193V931 081 91V933919V 33V1LV1999 1391139V3V 9319VW999 33W3W933 19939V193V 021 391939V33V 911999WW 3V9391V91L 39319V399V 31V9V93393 1331393933 09 33V9331939 93V93339V9 1933311919 99V3W99V9 3391V9133V W933931L3 ■ 8I -0N QI D3S - NOIldlHOSBα 33N3003S ( PO JBΘU L L :A9010d01 (0) θLδu p : sS3Nα3αNVHlS (3) ppB o p pnu : 3 Al (8) s LBd 3S q 28H : H19N31 (V) : S3IlSiy313VWH333N3003S (!■) : 8I : 0N 0103$ aOd NOUVWHOdNI (2) 2Z8I 1131LV933V39 0981 913V13N1L9 V3V933933191331V93JJL V319913W9319V9W933 V3V931931L 008T 31V31V9933393V933V3V 13939V939V 33V3V939V9919193V1LV 13V91993V1 Oni 933V993V9V 333V93933933319V99V3 JJJL9913333 V39319V993133V3V31W 0891 91V9199133 V933V31V31 V39331V199 V939933V313933V3V9319913339319 ζ9 „ , r ^ ¥ 8Zfr60/£6 OM PL9Pl/96SLVlDd 09 11999V9313 991V9V33V9 3399393399 9131L39V1V 9399339V93 V39931LW9 : 6T : ON QI D3S - NOUdldOSBα 33N3D03S ( LX) JP3U L L :A9010d01 (0) Θ | 6U LS : sS3N03αNVai (3) ppB o p nu : 3dAl (8) sJ LBd θsεq 9/8 -Η19N31 (V) : S3IlSiy313VaVH3 33N3HD3S U) : 6I : 0N 01 03S dOd NOUVWyOdNI (2) 28H 19 1131391W3 1LL39V9991 999V393V31 3V913V3V99 Om 9339V33993 1V93939993 9399313119 V331399193 1L31LV199V 3399399V39 0881 9V39139333 1L3V3V9139 9933313V99 91V33V33V3 133399391V 9939399399 0281 939W99933 W9331L3V9 3W331L313 W9319VW3 1391V39V93 V3399V911L 092T 9393191991 V939191V9V 33391999V3 31VW91V91 9939993931 V1193V93V3 002T WVW33399 99399V3391 9933311319 V91V9W393 3V93399V33 931V193939 OH I 3V3V913399 33V91V9333 V39V3W939 9199399399 31LV333V13 91933W939 0801 931339V919 9193993339 391V9V1939 93119V9199 933VW3399 39V1V9939V 0201 99V33V33W 3193113V93 3W191W99 3VW313999 3133993991 199V9W9W 096 99139V33V3 V99V99933V 1V31393339 9139W31V9 3V9193V991 1V113399W 006 9339933V33 3393133VW V933933931 93193V93W 39V3993991 V31V931993 Q B 99V93V9919 91V39V3113 V93V93999V 9111339319 139V199339 V911L31993 08Z 93199V9339 9393V99919 9139933119 919931L31L V1L991991L 99399933V9 02Z V133333V91 1WW9131V 399DV91333 33V913WW 9333V3993V V3191993W 099 9191133393 VW9313911 9393V93193 9119W9339 9V13V93193 W319333W 99 PL9PΪ/96SΩJ10d 8W50/..6 OΛV CGTGCTCGGG GCCACCGCCG GGCGCACCAC CCTGACCGGT GAGGGCCTGC AACACGCCGA 120 CGGTCACTCG TJGCTGCTGG ACGCCACCAA CCCGGCGGTG GπGCCTACG ACCCGGCCTT 180 CGCCTACGAA ATCGGCTACA TCGNGGAAAG CGGACTGGCC AGGATGTGCG GGGAGAACCC 240 GGAGAACATC πcπCTACA TCACCGTCTA CAACGAGCCG TACGTGCAGC CGCCGGAGCC 300 GGAGAACπC GATCCCGAGG GCGTGCTGGG GGGTATCTAC CGNTATCACG CGGCCACCGA 360 GCAACGCACC AACAAGGNGC AGATCCTGGC CTCCGGGGTA GCGATGCCCG CGGCGCTGCG 420 GGCAGCACAG ATGCTGGCCG CCGAGTGGGA TGTCGCCGCC GACGTGTGGT CGGTGACCAG 480 πGGGGCGAG CTAAACCGCG ACGGGGTGGT CATCGAGACC GAGAAGCTCC GCCACCCCGA 540 TCGGCCGGCG GGCGTGCCCT ACGTGACGAG AGCGCTGGAG AATGCTCGGG GCCCGGTGAT 600 CGCGGTGTCG GACTGGATGC GCGCGGTCCC CGAGCAGATC CGACCGTGGG TGCCGGGCAC 660 ATACCTCACG πGGGCACCG ACGGGπCGG ππTCCGAC ACTCGGCCCG CCGGTCGTCG 720 πACπCAAC ACCGACGCCG AATCCCAGGT TGGTCGCGGT TiTGGGAGGG GπGGCCGGG 780 TCGACGGGTG AATATCGACC CAπCGGTGC CGGTCGTGGG CCGCCCGCCC AGπACCCGG 840 AπCGACGAA GGTGGGGGGT TGCGCCCGAN TAAGπ 876 (2) INFORMATION FOR SEQ ID NO : 20 : (i ) SEQUENCE CHARACTERISTICS : (A) LENGTH : 1021 base pai rs (B) TYPE : nucl ei c aci d (C) STRANDEDNESS : si ngl e (D) TOPOLOGY : l i near (xi ) SEQUENCE DESCRIPTION : SEQ ID NO : 20 : ATCCCCCCGG GCTGCAGGAA πCGGCACGA GAGACAAAAT TCCACGCGπ AATGCAGGAA 60 B9ULL :λSO OdOl (0) 3 L6U LS : sS Nα3αNVdlS (3) p pB o nu : 3dAl (8) s LBd θSBq I2C : H19N31 (V) : S3USId313VWH3 33N3fl03S U) : I2 : 0N 01 Q3S dOd NOIlVWdOd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g 3391393V3933339399V31V393399339399191V9919W9193V393193113W 0817 9V9V139V931L9133W3399993399931V93391L999391991333 W3991V911 02fr 3399199V9V V931V9V3W 99V39113119919V391V3119V39V939931331LLV9 098 3999V93V9393339919939V3V9139931993199V33 V933V319V3 V393W99V3 008 1V9313939913939913V399V9393333 V9V3V931L9 V33VW9391993V3V9V19 0172 3993331LW V93191931133V93933V93139133V3V V391931391 V91W391V3 081 3VW93W99 V9319939W 339V3V1LU 1V39W9399119V39339133V9W939V 021 3V931LLV111993931V9393191V1W3 W3V39939V 3V31LW93V V1V31LV9V3 89 PL9Pl/96SΛ/lDd KP60/ 6 O/A (xi) SEQUENCE DESCRIPTION: SEQ ID NO:21: CGTGCCGACG AACGGAAGAA CACAACCATG AAGATGGTGA AATCGATCGC CGCAGGTCTG 60 ACCGCCGCGG CTGCAATCGG CGCCGCTGCG GCCGGTGTGA CπCGATCAT GGCTGGCGGN 120 CCGGTCGTAT ACCAGATGCA GCCGGTCGTC πCGGCGCGC CACTGCCGπ GGACCCGGNA 180 TCCGCCCCTG ANGTCCCGAC CGCCGCCCAG TGGACCAGNC TGCTCAACAG NCTCGNCGAT 240 CCCAACGTGT CGTπGNGAA CAAGGGNAGT CTGGTCGAGG GNGGNATCGG NGGNANCGAG 300 GGNGNGNATC GNCGANCACA A 321 (2) INFORMATION FOR SEQ ID NO:22: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 373 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID N0:22: TCπATCGGT TCCGGπGGC GACGGGππ GGGNGCGGGT GGπAACCCG CTCGGCCAGC 60 CGATCGACGG GCGCGGAGAC GTCGACTCCG ATACTCGGCG CGCGCTGGAG CTCCAGGCGC 120 CCTCGGTGGT GNACCGGCAA GGCGTGAAGG AGCCGπGNA GACCGGGATC AAGGCGAπG 180 ACGCGATGAC CCCGATCGGC CGCGGGCAGC GCCAGCTGAT CATCGGGGAC CGCAAGACCG 240 GCAAAAACCG CCGTCTGTGT CGGACACCAT CCTCAAACCA GCGGGAAGAA CTGGGAGTCC 300 GGTGGATCCC AAGAAGCAGG TGCGCπGTG TATACGπGG CCATCGGGCA AGAAGGGGAA 360 CTTACCATCG CCG 373 (2) INFORMATION FOR SEQ ID N0:23: 0172 931999931319993991919993V33991331V39193993991391V31393V39339 08T 19393119933V191V3931 V31933V1931LL3931V9V 3391139119 V331939V13 02T 3V3931V1V19913131L9V V39V31W19 V939V3V319991V3139399393119939 09 339W31V919W93V931V V1V9399139939V33V93119331LV31L 939331VW9 :i72 : ON QI 03S - ' NOIldlrdDSBα 33N3003S ( PO JBΘULL -A9010d01 (0) Θ[6ULS :sS3Nα αNVdlS (3) ppB Dppnu :3dAl (9) s LBd θSBq 92Z : H19N31 (V) : S0IlSId313VdVH333N3003S Q) : 1?2-0N 01 03S dOd NOIlVWdOdNI (2) 258 V9 V99NV9331L 9W93N1V3V 3N3331LV9N 9931V1V33N V93V93V9JJL 008 19N9N1V33939391393V3 V99919WN9919339V33933V3193ULL 199V991939 01 99919V33931399139V391913993991 V39991919939933V1993 391V331V91 081 3919931W93999399W31V9V9339V111V933991L 9993V19913 3993V91L31 021 1919919933919139339V 399V3139111931991399 W393391999333V1L991 09 3W39V31V991991993991393319933 999939991331LV9991V9193393V919 : 82-0N 01 03S NOIldldOSdQ 33N3nθ3S ( PO J59ULL :A9010d01 (0) θL β up :sS3Nα3αNVd!S (3) PPB oppnu :3dAl (8) s j LBd ΘS q 29G :H19N31 (V) :S3USId313V>JVH333N3DD3S Q) oz PL9P\/96SlΛllDd 8ZP60/L6 OM GCGCGCAGTC CGCAGCCCAA ACCGCGCCGG TGCCCGACTA CTACTGGTGC CCGGGGCAGC 300 CTTTCGACCC CGCATGGGGG CCCAACTGGG ATCCCTACAC CTGCCATGAC GACπCCACC 360 GCGACAGCGA CGGCCCCGAC CACAGCCGCG ACTACCCCGG ACCCATCCTC GAAGGTCCCG 420 TGCπGACGA TCCCGGTGCT GCGCCGCCGC CCCCGGCTGC CGGTGGCGGC GCATAGCGCT 480 CGπGACCGG GCCGCATCAG CGAATACGCG TATAAACCCG GGCGTGCCCC CGGCAAGCTA 540 CGACCCCCGG CGGGGCAGAT πACGCTCCC GTGCCGATGG ATCGCGCCGT CCGATGACAG 600 AAAATAGGCG ACGGTπTGG CAACCGCπG GAGGACGCπ GAAGGGAACC TGTCATGAAC 660 GGCGACAGCG CCTCCACCAT CGACATCGAC AAGGπGπA CCCGCACACC CGπCGCCGG 720 ATCGTG 726 (2) INFORMATION FOR SEQ ID NO: 25 : ( i ) SEQUENCE CHARACTERISTICS : (A) LENGTH : 580 base pai rs (B) TYPE : nucl ei c aci d (C) STRANDEDNESS : si ngl e (D) TOPOLOGY : l i near (xi ) SEQUENCE DESCRIPTION : SEQ ID N0 : 25 : CGCGACGACG ACGAACGTCG GGCCCACCAC CGCCTATGCG πGATGCAGG CGACCGGGAT 60 GGTCGCCGAC CATATCCAAG CATGCTGGGT GCCCACTGAG CGACCTTTTG ACCAGCCGGG 120 CTGCCCGATG GCGGCCCGGT GAAGTCAπG CGCCGGGGCT TGTGCACCTG ATGAACCCGA 180 ATAGGGAACA ATAGGGGGGT GATTTGGCAG πCAATGTCG GGTATGGCTG GAAATCCAAT 240 GGCGGGGCAT GCTCGGCGCC GACCAGGCTC GCGCAGGCGG GCCAGCCCGA ATCTGGAGGG 300 AGCACTCAAT GGCGGCGATG AAGCCCCGGA CCGGCGACGG TCCπTGGAA GCAACTAAGG 360 02T 3391399399 V99393H9333399391V939931V33V9193993V9333V3V3939V3 09 31V93V3119399V931393 V3V93191193W3393V191V91991V93 V1V933V3V9 :Z2 : 0 QI 03S : NOIldIdOS3Q 33N3fl03S (LX) JB9U L : A90 ~ IOd01 (0) ΘLSULS : SS3N03αNVdlS (3) ppB DLΘLDΠU :3dAl (8) SJLBd θsεq HZ :H19N31 (V) •' S0IlSId313VdVH333N3D03S U) ■ LZ- ON 01 03S dOd NOUVWdOdNI (2) 091 9331V99199933V3V39V33993193V19993V319199 021 33931V3993 W399V9933999919933999939931919931191199933933V199 09 3993399993993W399399319939999339999399111199999339399V993W :92 : 0N QI 03S : NOIldId3S3Q 33N3003S ( PO JBΘULL :A90 " 10d01 (0) a[ β uLS : SSBNOdαNVdlS (3) ppB op nu :3 l (9) SJLBd θ Bq 091 -H19N3 (V) • S3IlSId313VWH333N3n03S U) : 92 : ON OI DBS dOd NOUVWdOdNI (2) 08S 13939V3V1V 991L313W9 V99V33391V 191V939931 01 7 9 39131919V33191V9V199331L33V3V39393V11939931991W9D 993W3339V 08t 7 33V9W139V 13V1L9399V W313W93V 9199913V39339339W93 V9333V3V91 0217 39V93193199133931993991999V91L 3V33V19V9391V9191LV3993939999V ZL PL9PimSVlDd KWO/tfOM JBΘULL :A9010d01 (0) θL β up :sS3Nα3αNVd!S (3) ppB o nu : Al (8) SJLBd θsεq 28T :H19N31 (V) : S3IlSIH313VdVH333N3H03S U) • 62 : 0N 01 03 S dOd NOUVWdOdNI (2) ZI8 99939391199133993 008 931139919V 3V93193193 V331V9VW319939W9W 31V9W93933V9131W99 OPZ 39319913393339133931 V3V199131V 131993V9V93119919399131V9931L9 08T 331V93V9999393V931999931V319993939939W93399193W9139V99V393 021 933V31V1393399133V13 9391V3119939339133931V993V9V39 V931V9939V 09 V9139V93939193V93939 V393V91993 V3939131V13V993131L99199339V39 :82 : 0N QI D3S :NOIldIdOS3Q 33N3DD3S (!*x) JBΘULL :A9010d01 (CO ΘL6ULS : S3Nα3αNVdlS (3) ppB oppnu ; 3dλl (g) SJLBd θSBq /ie -H19N31 (V) : S3IlSId313VdVH333N3HD3S Q) : 82-ON OI D3S dOd NOUVWdOdNI (2) ZLZ 93 3393W33V9 V3V193W3939V93V1339 0172 31911931919933333991193991L93V 3W3W3993 V90V99919V 3W9393W9 081 1393193193333V991W9933V1V31LV V199939139 W3V931W9991V9399W £L PL9Pl/96Sll/lDd 8Zfr60/t-6 OM 74 (xi ) SEQUENCE DESCRIPTION : SEQ ID N0: 29 : GATCGTGGAG CTGTCGATGA ACAGCGπGC CGGACGCGCG GCGGCCAGCA CGTCGGTGTA 60 GCAGCGCCGG ACCACCTCGC CGGTGGGCAG CATGGTGATG ACCACGTCGG CCTCGGCCAC 120 CGCπCGGGC GCGCTACGAA ACACCGCGAC ACCGTGCGCG GCGGCGCCGG ACGCCGCCGT 180 GG 182 (2) INFORMATION FOR SEQ ID NO : 30 : ( i ) SEQUENCE CHARACTERISTICS : (A) LENGTH: 308 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY : l i near (xi ) SEQUENCE DESCRIPTION : SEQ ID N0: 30 : GATCGCGAAG TTTGGTGAGC AGGTGGTCGA CGCGAAAGTC TGGGCGCCTG CGAAGCGGGT 60 CGGCGπCAC GAGGCGAAGA CACGCCTGTC CGAGCTGCTG CGGCTCGTCT ACGGCGGGCA 120 GAGGπGAGA πGCCCGCCG CGGCGAGCCG GTAGCAAAGC πGTGCCGCT GCATCCTCAT 180 GAGACTCGGC GGπAGGCAT TGACCATGGC GTGTACCGCG TGCCCGACGA TπGGACGCT 240 CCGπGTCAG ACGACGTGCT CGAACGCTπ CACCGGTGAA GCGCTACCTC ATCGACACCC 300 ACGTπGG 308 (2) INFORMATION FOR SEQ ID NO:31: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 267 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID N0:31: CCGACGACGA GCAACTCACG TGGATGATGG TCGGCAGCGG CAπGAGGAC GGAGAGAATC 60 CGGCCGAAGC TGCCGCGCGG CAAGTGCTCA TAGTGACCGG CCGTAGAGGG CTCCCCCGAT 120 GGCACCGGAC TAπCTGGTG TGCCGCTGGC CGGTAAGAGC GGGTAAAAGA ATGTGAGGGG 180 ACACGATGAG CAATCACACC TACCGAGTGA TCGAGATCGT CGGGACCTCG CCCGACGGCG 240 TCGACGCGGC AATCCAGGGC GGTCTGG 267 (2) INFORMATION FOR SEQ ID NO: 32: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 189 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID NO:32: CTCGTGCCGA AAGAATGTGA GGGGACACGA TGAGCAATCA CACCTACCGA GTGATCGAGA 60 TCGTCGGGAC CTCGCCCGAC GGCGTCGACG CGGCAATCCA GGGCGGTCTG GCCCGAGCTG 120 CGCAGACCAT GCGCGCGCTG GACTGGπCG AAGTACAGTC AAπCGAGGC CACCTGGTCG 180 ACGGAGCGG 189 (2) INFORMATION FOR SEQ ID NO: 33: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 851 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear 76 (xi) SEQUENCE DESCRIPTION: SEQ ID N0:33: CTGCAGGGTG GCGTGGATGA GCGTCACCGC GGGGCAGGCC GAGCTGACCG CCGCCCAGGT 60 CCGGGπGCT GCGGCGGCCT ACGAGACGGC GTATGGGCTG ACGGTGCCCC CGCCGGTGAT 120 CGCCGAGAAC CGTGCTGAAC TGATGAπCT GATAGCGACC AACCTCπGG GGCAAAACAC 180 CCCGGCGATC GCGGTCAACG AGGCCGAATA CGGCGAGATG TGGGCCCAAG ACGCCGCCGC 240 GATGTπGGC TACGCCGCGG CGACGGCGAC GGCGACGGCG ACGπGCTGC CGπCGAGGA 300 GGCGCCGGAG ATGACCAGCG CGGGTGGGCT CCTCGAGCAG GCCGCCGCGG TCGAGGAGGC 360 CTCCGACACC GCCGCGGCGA ACCAGπGAT GAACAATGTG CCCCAGGCGC TGAAACAGπ 420 i GGCCCAGCCC ACGCAGGGCA CCACGCCπC πCCAAGCTG GGTGGCCTGT GGAAGACGGT 480 CTCGCCGCAT CGGTCGCCGA TCAGCAACAT GGTGTCGATG GCCAACAACC ACATGTCGAT 540 GACCAACTCG GGTGTGTCGA TGACCAACAC CπGAGCTCG ATGπGAAGG GCTπGCTCC 600 GGCGGCGGCC GCCCAGGCCG TGCAAACCGC GGCGCAAAAC GGGGTCCGGG CGATGAGCTC 660 GCTGGGCAGC TCGCTGGGπ CπCGGGTCT GGGCGGTGGG GTGGCCGCCA ACπGGGTCG 720 GGCGGCCTCG GTACGGTATG GTCACCGGGA TGGCGGAAAA TATGCANAGT CTGGTCGGCG 780 GAACGGTGGT CCGGCGTAAG GTπACCCCC GππCTGGA TGCGGTGAAC πCGTCAACG 840 GAAACAGπA C 851 (2) INFORMATION FOR SEQ ID N0:34 : ( i ) SEQUENCE CHARACTERISTICS : (A) LENGTH : 254 base pai rs (B) TYPE : nucl ei c aci d (C) STRANDEDNESS : si ngl e (D) TOPOLOGY : l i near (xi) SEQUENCE DESCRIPTION: SEQ ID N0:34: GATCGATCGG GCGGAAATπ GGACCAGAπ CGCCTCCGGC GATAACCCAA TCAATCGAAC 60 CTAGAπTAT TCCGTCCAGG GGCCCGAGTA ATGGCTCGCA GGAGAGGAAC CπACTGCTG 120 CGGGCACCTG TCGTAGGTCC TCGATACGGC GGAAGGCGTC GACATπTCC ACCGACACCC 180 CCATCCAAAC GπCGAGGGC CACTCCAGCT TGTGAGCGAG GCGACGCAGT CGCAGGCTGC 240 GCπGGTCAA GATC 254 (2) INFORMATION FOR SEQ ID N0:35: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 408 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID NO:35: CGGCACGAGG ATCCTGACCG AAGCGGCCGC CGCCAAGGCG AAGTCGCTGT TGGACCAGGA 60 GGGACGGGAC GATCTGGCGC TGCGGATCGC GGπCAGCCG GGGGGGTGCG CTGGAπGCG 120 CTATAACCπ πcπCGACG ACCGGACGCT GGATGGTGAC CAAACCGCGG AGπCGGTGG 180 TGTCAGGπG ATCGTGGACC GGATGAGCGC GCCGTATGTG GAAGGCGCGT CGATCGATπ 240 CGTCGACACT AπGAGAAGC AAGGNπCAC CATCGACAAT CCCAACGCCA CCGGCTCCTG 300 CGCGTGCGGG GAπCGπCA ACTGATAAAA CGCTAGTACG ACCCCGCGGT GCGCAACACG 360 TACGAGCACA CCAAGACCTG ACCGCGCTGG AAAAGCAACT GAGCGATG 408 (2) INFORMATION FOR SEQ ID NO: 36: (i) SEQUENCE CHARACTERISTICS: • 88-ON 01 03S dOd NOUVWdOdNI (2) 062 3V91993993 V91993993V 9199N99313 39933V9393 9V9V313V39 0172 9399399UV N993999V33 991999W19 93993W3991993U3993 993V993333 081 93W399V99 3991993999 39399399U 31993993W 39939933V3 3139939939 021 91W399399 9V39991993 133993999V 33993993391993391113 193993V939 09 93999933993993191993 993W3993V V9U991999 399331V993 9931919939 • Z8-ON QI 03S : N0UdId3S3α 33N3fl03S (PO JP3ULL -AOOTOdOl (0) ΘL6U S :SS3Nα3αNVdlS (3) ppB D.LΘLDΠU :3dAl (a) SJLBd ΘSBq 062 :H19N31 (V) : S3IlSId313VdVH3 33N3nθ3S U) ■ l£-θn 01 DBS dOd NOUVWdOdNI (2) I8T 9 081 93993W399 3V13191 V 9939933199 9399319N991991W33V3 99339N9939 021 9331999399 3399993U9 9910393V V3993993391991993W1 3939933V99 09 93993399993993399993 993W3993V V9U991999 399331V993 9931919939 : 9ε- ' 0N QI DBS -NOIldiaOSBQ 33N3003S (PO JBΘULL -AOOIOdOl (0) θLδULS :sS3N03αNVdlS (3) ppB DLΘLDΠU : l (a) SJLBd ΘSBq T8I :H19N31 (V) 8Z 8Zf 60/.6 OM PL9Pl/96SO/lDd (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 34 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID N0:38: GATCCAGTGG CATGGNGGGT GTCAGTGGAA GCAT 34 (2) INFORMATION FOR SEQ ID NO:39: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 155 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID N0:39: GATCGCTGCT CGTCCCCCCC πGCCGCCGA CGCCACCGGT CCCACCGπA CCGAACAAGC 60 TGGCGTGGTC GCCAGCACCC CCGGCACCGC CGACGCCGGA GTCGAACAAT GGCACCGTCG 120 TATCCCCACC AπGCCGCCG GNCCCACCGG CACCG 155 (2) INFORMATION FOR SEQ ID NO:40: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 53 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID N0:40: ATGGCGπCA CGGGGCGCCG GGGACCGGGC AGCCCGGNGG GGCCGGGGGG TGG 53 (2) INFORMATION FOR SEQ ID NO:41: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 132 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID NO:41: GATCCACCGC GGGTGCAGAC GGTGCCCGCG GCGCCACCCC GACCAGCGGC GGCAACGGCG 60 GCACCGGCGG CAACGGCGCG AACGCCACCG TCGTCGGNGG GGCCGGCGGG GCCGGCGGCA 120 AGGGCGGCAA CG 132 (2) INFORMATION FOR SEQ ID N0:42: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 132 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID N0:42: GATCGGCGGC CGGNACGGNC GGGGACGGCG GCAAGGGCGG NAACGGGGGC GCCGNAGCCA 60 CCNGCCAAGA ATCCTCCGNG TCCNCCAATG GCGCGAATGG CGGACAGGGC GGCAACGGCG 120 GCANCGGCGG CA 132 81 (2) INFORMATION FOR SEQ ID N0:43: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 702 base pairs (LD TYPE: nucleic acid (C) STRANDEDNESS : single (D) TOPOLOGY : l i near (xi) SEQUENCE DESCRIPTION: SEQ ID N0:43: CGGCACGAGG ATCGGTACCC CGCGGCATCG GCAGCTGCCG AπCGCCGGG πTCCCCACC 60 CGAGGAAAGC CGCTACCAGA TGGCGCTGCC GAAGTAGGGC GATCCGπCG CGATGCCGGC 120 ATGAACGGGC GGCATCAAAT TAGTGCAGGA ACCTπCAGT πAGCGACGA TAATGGCTAT 180 AGCACTAAGG AGGATGATCC GATATGACGC AGTCGCAGAC CGTGACGGTG GATCAGCAAG 240 AGATTTTGAA CAGGGCCAAC GAGGTGGAGG CCCCGATGGC GGACCCACCG ACTGATGTCC 300 CCATCACACC GTGCGAACTC ACGGNGGNTA AAAACGCCGC CCAACAGNTG GTNπGTCCG 360 CCGACAACAT GCGGGAATAC CTGGCGGCCG GTGCCAAAGA GCGGCAGCGT CTGGCGACCT 420 CGCTGCGCAA CGCGGCCAAG GNGTATGGCG AGGπGATGA GGAGGCTGCG ACCGCGCTGG 480 ACAACGACGG CGAAGGAACT GTGCAGGCAG AATCGGCCGG GGCCGTCGGA GGGGACAGπ 540 CGGCCGAACT AACCGATACG CCGAGGGTGG CCACGGCCGG TGAACCCAAC πCATGGATC 600 TCAAAGAAGC GGCAAGGAAG CTCGAAACGG GCGACCAAGG CGCATCGCTC GCGCACTGNG 660 GGGATGGGTG GAACACπNC ACCCTGACGC TGCAAGGCGA CG 702 (2) INFORMATION FOR SEQ ID NO:44: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 298 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (xi ) SEQUENCE DESCRIPTION: SEQ ID N0 : 44 : GAAGCCGCAG CGCTGTCGGG CGACGTGGCG GTCAAAGCGG CATCGCTCGG TGGCGGTGGA "60 GGCGGCGGGG TGCCGTCGGC GCCGπGGGA TCCGCGATCG GGGGCGCCGA ATCGGTGCGG 120 CCCGCTGGCG CTGGTGACAT TGCCGGCTTA GGCCAGGGAA GGGCCGGCGG CGGCGCCGCG 180 CTGGGCGGCG GTGGCATGGG AATGCCGATG GGTGCCGCGC ATCAGGGACA AGGGGGCGCC 240 AAGTCCAAGG GπCTCAGCA GGAAGACGAG GCGCTCTACA CCGAGGATCC TCGTGCCG 298 (2) INFORMATION FOR SEQ ID N0:45 : ( i ) SEQUENCE CHARACTERISTICS : (A) LENGTH : 1058 base pai rs (B) TYPE : nuclei c acid (C) STRANDEDNESS : single (D) TOPOLOGY: l i near (xi ) SEQUENCE DESCRIPTION: SEQ ID N0: 45 : CGGCACGAGG ATCGAATCGC GTCGCCGGGA GCACAGCGTC GCACTGCACC AGTGGAGGAG 60 CCATGACCTA CTCGCCGGGT AACCCCGGAT ACCCGCAAGC GCAGCCCGCA GGCTCCTACG 120 GAGGCGTCAC ACCCTCGπC GCCCACGCCG ATGAGGGTGC GAGCAAGCTA CCGATGTACC 180 TGAACATCGC GGTGGCAGTG CTCGGTCTGG CTGCGTACπ CGCCAGCπC GGCCCAATGT 240 TCACCCTCAG TACCGAACTC GGGGGGGGTG ATGGCGCAGT GTCCGGTGAC ACTGGGCTGC 300 CGGTCGGGGT GGCTCTGCTG GCTGCGCTGC πGCCGGGGT GGπCTGGTG CCTAAGGCCA 360 AGAGCCATGT GACGGTAGπ GCGGTGCTCG GGGTACTCGG CGTATTTCTG ATGGTCTCGG 420 008 3V913U39991VW39313319139399V 39V39V39V99V93V933999V9313V1W 017 33193993399V3193UV1 W93V93131 V9V93V9313 W99V39W9 V39W1W33 081 9V39W9W33U3939199199393399V 333933993V 9999399393993939919V 02T 33999V39U 93U99V3993V9319V99199V33V931V 9V333WW9133V939933 09 131V9939V931UW199V 399V99V393931333V1393391V933V9 V9V93V3993 • 917-ON QI D3S -NOIldldOSBQ 33N3flD3S (!*x) JBΘULL : A9010d01 (0) ΘLSULS :sS3NαBONVdlS (3) ppB DpL-^nu :3dAl (9) J LBd ΘSBq LZZ : H19N31 (V) : S3IlSId313VdVH3 33N3nθ3S U ) : 9HON 01 D3S dOd NOUVWdOdNI (2) 8501 3UW933 91931331V9 3V993939W 39V3191999 020 T V3W919V9V V939391919 3939319933 1939333U9 399933W13 1993393999 096 9999333331 9319319V39 V939999939 V3333VW31 1V13W319V 3313993U9 006 91399V3931 99993V9993 3919V31993 3V33V33V33 39V3U39V9 3311139933 0178 V133V3393V 331V333999 V33V3931W 3W3931999 3319V39399 339339V333 08Z 99333339V3 13913V3V1V 9919V39993 1W339V933 19V33193U V13993993V 02Z 19V3931999 1V1V993331 339V393313 19V39V3933 3993339319 V3913V9993 099 93399V39V3 1391999V39 V31993V13V 1999199933 9V39199993 V19V39993V 009 19V39993V1 9939993V19 V3V991V193 33V93U9W 3339939339 3993393933 0175 V31V139399 33V9V99199 U31393991 3319V39939 U99399V33 U91931V31 0817 U399U919 U99919UV 3999U9933 V93UV1339 39V3339W3 WJJ 93V93 £8 P L9P V96SiVlDd 8Zf 60//.6 OM CCGCTAATAC GAAAAGAAAC GGAGCAA 327 (2) INFORMATION FOR SEQ ID NO:47: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 170 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID N0:47: CGGTCGCGAT GATGGCGπG TCGAACGTGA CCGAπCTGT ACCGCCGTCG πGAGATCAA 60 CCAACAACGT GπGGCGTCG GCAAATGTGC CGNACCCGTG GATCTCGGTG ATCπGπCT 120 TCπCATCAG GAAGTGCACA CCGGCCACCC TGCCCTCGGN TACCTπCGG 170 (2) INFORMATION FOR SEQ ID N0:48: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 127 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID N0:48: GATCCGGCGG CACGGGGGGT GCCGGCGGCA GCACCGCTGG CGCTGGCGGC AACGGCGGGG 60 CCGGGGGTGG CGGCGGAACC GGTGGGπGC TCπCGGCAA CGGCGGTGCC GGCGGGCACG 120 GGGCCGT 127 (2) INFORMATION FOR SEQ ID N0:49: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 81 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (CT) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID N0:49: CGGCGGCAAG GGCGGCACCG CCGGCAACGG GAGCGGCGCG GCCGGCGGCA ACGGCGGCAA 60 CGGCGGCTCC GGC ' JCAACG G 81 (2) INFORMATION FOR SEQ ID NO:50: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 149 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID NO:50: GATCAGGGCT GGCCGGCTCC GGCCAGAAGG GCGGTAACGG AGGAGCTGCC GGAπGπTG 60 GCAACGGCGG GGCCGGNGGT GCCGGCGCGT CCAACCAAGC CGGTAACGGC GGNGCCGGCG 120 GAAACGGTGG TGCCGGTGGG CTGATCTGG 149 (2) INFORMATION FOR SEQ ID NO:51: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 355 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID N0:51: CGGCACGAGA TCACACCTAC CGAGTGATCG AGATCGTCGG GACCTCGCCC GACGGTGTCG 60 ACGCGGNAAT CCAGGGCGGT CTGGCCCGAG CTGCGCAGAC CATGCGCGCG CTGGACTGGT 120 TCGAAGTACA GTCAAπCGA GGCCACCTGG TCGACGGAGC GGTCGCGCAC πCCAGGTGA 180 CTATGAAAGT CGGCπCCGC CTGGAGGAπ CCTGAACCπ CAAGCGCGGC CGATAACTGA 240 GGTGCATCAT TAAGCGACπ πCCAGAACA TCCTGACGCG CTCGAAACGC GGπCAGCCG 300 ACGGTGGCTC CGCCGAGGCG CTGCCTCCAA AATCCCTGCG ACAAπCGTC GGCGG 355 (2) INFORMATION FOR SEQ ID NO:52: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 999 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (xi ) SEQUENCE DESCRIPTION : SEQ ID N0: 52: ATGCATCACC ATCACCATCA CATGCATCAG GTGGACCCCA ACπGACACG TCGCAAGGGA 60 CGAπGGCGG CACTGGCTAT CGCGGCGATG GCCAGCGCCA GCCTGGTGAC CGπGCGGTG 120 CCCGCGACCG CCAACGCCGA TCCGGAGCCA GCGCCCCCGG TACCCACAAC GGCCGCCTCG 180 CCGCCGTCGA CCGCTGCAGC GCCACCCGCA CCGGCGACAC CTGπGCCCC CCCACCACCG 240 GCCGCCGCCA ACACGCCGAA TGCCCAGCCG GGCGATCCCA ACGCAGCACC TCCGCCGGCC 300 GACCCGAACG CACCGCCGCC ACCTGTCAπ GCCCCAAACG CACCCCAACC TGTCCGGATC 360 GACAACCCGG πGGAGGAπ CAGCπCGCG CTGCCTGCTG GCTGGGTGGA GTCTGACGCC 420 GCCCACπCG ACTACGGπC AGCACTCCTC AGCAAAACCA CCGGGGACCC GCCATπCCC 480 GGACAGCCGC CGCCGGTGGC CAATGACACC CGTATCGTGC TCGGCCGGCT AGACCAAAAG 540 CTπACGCCA GCGCCGAAGC CACCGACTCC AAGGCCGCGG CCCGGπGGG CTCGGACATG 600 GGTGAGπCT ATATGCCCTA CCCGGGCACC CGGATCAACC AGGAAACCGT CTCGCTCGAC 660 GCCAACGGGG TGTCTGGAAG CGCGTCGTAT TACGAAGTCA AGπCAGCGA TCCGAGTAAG 720 CCGAACGGCC AGATCTGGAC GGGCGTAATC GGCTCGCCCG CGGCGAACGC ACCGGACGCC 780 GGGCCCCCTC AGCGCTGGπ TGTGGTATGG CTCGGGACCG CCAACAACCC GGTGGACAAG 840 GGCGCGGCCA AGGCGCTGGC CGAATCGATC CGGCCTπGG TCGCCCCGCC GCCGGCGCCG 900 GCACCGGCTC CTGCAGAGCC CGCTCCGGCG CCGGCGCCGG CCGGGGAAGT CGCTCCTACC 960 CCGACGACAC CGACACCGCA GCGGACCπA CCGGCCTGA 999 (2) INFORMATION FOR SEQ ID NO:53: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 332 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID NO:53: Met His His His His His His Met His Gin Val Asp Pro Asn Leu Thr 1 5 10 15 Arg Arg Lys Gly Arg Leu Ala Ala Leu Ala Ile Ala Ala Met Ala Ser 20 25 30 Al a Ser Leu Val Thr Val Al a Val Pro Ala Thr Ala Asn Ala Asp Pro 35 40 45 Gl u Pro Ala Pro Pro Val Pro Thr Thr Ala Ala Ser Pro Pro Ser Thr 50 55 60 Ala Ala Ala Pro Pro Ala Pro Ala Thr Pro Val Ala Pro Pro Pro Pro 65 70 75 80 Ala Ala " Ala Asn Thr Pro Asn Ala Gin Pro Gly Asp Pro Asn Ala Ala 85 90 95 Pro Pro Pro Ala Asp Pro Asn Ala Pro Pro Pro Pro Val He Ala Pro 100 105 110 Asn Ala Pro Gin Pro Val Arg He Asp Asn Pro Val Gly Gly Phe Ser 115 120 125 Phe Ala Leu Pro Ala Gly Trp Val Glu Ser Asp Ala Ala His Phe Asp 130 135 140 Tyr Gly Ser Ala Leu Leu Ser Lys Thr Thr Gly Asp Pro Pro Phe Pro 145 150 155 160 Gly Gin Pro Pro Pro Val Ala Asn Asp Thr Arg He Val Leu Gly Arg 165 170 175 Leu Asp Gin Lys Leu Tyr Ala Ser Ala Glu Ala Thr Asp Ser Lys Ala 180 185 190 Ala Ala Arg Leu Gly Ser Asp Met Gly Glu Phe Tyr Met Pro Tyr Pro 195 200 205 Gly Thr Arg Ile Asn Gin Glu Thr Val Ser Leu Asp Ala Asn Gly Val 210 215 220 Ser Gly Ser Ala Ser Tyr Tyr Glu Val Lys Phe Ser Asp Pro Ser Lys 225 230 235 240 Pro Asn Gly Gin Ile Trp Thr Gly Val He Gly Ser Pro Ala Ala Asn 245 250 255 Ala Pro Asp Ala Gly Pro Pro Gin Arg Trp Phe Val Val Trp Leu Gly 260 265 270 Thr Ala Asn Asn Pro Val Asp Lys Gly Ala Ala Lys Ala Leu Ala Glu 275 280 285 Ser He Arg Pro Leu Val Ala Pro Pro Pro Ala Pro Ala Pro Ala Pro 290 295 300 Ala Glu Pro Ala Pro Ala Pro Ala Pro Ala Gly Glu Val Ala Pro Thr 305 310 315 320 Pro Thr Thr Pro Thr Pro Gin Arg Thr Leu Pro Ala 325 330 (2) INFORMATION FOR SEQ ID NO:54: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 20 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID N0:54: Asp Pro Val Asp Ala Val Ile Asn Thr Thr Xaa Asn Tyr Gly Gin Val 1 5 10 15 Val Ala Ala Leu 20 (2) INFORMATION FOR SEQ ID NO:55: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 15 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID N0:55: Ala Val Glu Ser Gly Met Leu Ala Leu Gly Thr Pro Ala Pro Ser 1 5 10 15 (2) INFORMATION FOR SEQ ID N0:56: 90 (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 19 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID N0:56: Ala Ala Met Lys Pro Arg Thr Gly Asp Gly Pro Leu Glu Ala Ala Lys 1 5 10 15 Glu Gly Arg (2) INFORMATION FOR SEQ ID NO:57: (1) SEQUENCE CHARACTERISTICS: (A) LENGTH: 15 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID N0:57: Tyr Tyr Trp Cys Pro Gly Gin Pro Phe Asp Pro Ala Trp Gly Pro 1 5 10 15 (2) INFORMATION FOR SEQ ID NO:58: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 14 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID N0:58: Asp Ile Gly Ser Glu Ser Thr Glu Asp Gin Gin Xaa Ala Val 1 5 10 (2) INFORMATION FOR SEQ ID NO:59: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 13 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID N0:59: Ala Glu Glu Ser Ile Ser Thr Xaa Glu Xaa Ile Val Pro 1 5 10 (2) INFORMATION FOR SEQ ID NO:60: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 17 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID N0:60: Asp Pro Glu Pro Ala Pro Pro Val Pro Thr Ala Ala Ala Ala Pro Pro 1 5 10 15 Ala 92 (2) INFORMATION FOR SEQ ID NO:61: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 15 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: l i near (xi) SEQUENCE DESCRIPTION: SEQ ID N0:61: Ala Pro Lys Thr Tyr Xaa Glu Glu Leu Lys Gly Thr Asp Thr Gly 1 5 10 15 (2) INFORMATION FOR SEQ ID NO:62: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 30 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID NO:62: Asp Pro Ala Ser Ala Pro Asp Val Pro Thr Ala Ala Gin Gin Thr Ser 1 5 10 15 Leu Leu Asn Asn Leu Ala Asp Pro Asp Val Ser Phe Ala Asp 20 25 30 (2) INFORMATION FOR SEQ ID NO:63: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 187 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID NO:63: Thr Gly Ser Leu Asn Gin Thr His Asn Arg Arg Ala Asn Glu Arg Lys 1 5 10 15 Asn Thr Thr Met Lys Met Val Lys Ser Ile Ala Ala Gly Leu Thr Ala 20 25 30 Ala Ala Ala Ile Gly Ala Ala Ala Ala Gly Val Thr Ser Ile Met Ala 35 40 45 Gly Gly Pro Val Val Tyr Gin Met Gin Pro Val Val Phe Gly Ala Pro 50 55 60 Leu Pro Leu Asp Pro Ala Ser Ala Pro Asp Val Pro Thr Ala Ala Gin 65 70 75 80 Leu Thr Ser Leu Leu Asn Ser Leu Ala Asp Pro Asn Val Ser Phe Ala 85 90 95 Asn Lys Gly Ser Leu Val Glu Gly Gly Ile Gly Gly Thr Glu Ala Arg 100 105 110 Ile Ala Asp His Lys Leu Lys Lys Ala Ala Glu His Gly Asp Leu Pro 115 120 125 Leu Ser Phe Ser Val Thr Asn Ile Gin Pro Ala Ala Ala Gly Ser Ala 130 135 140 Thr Ala Asp Val Ser Val Ser Gly Pro Lys Leu Ser Ser Pro Val Thr 145 150 155 160 Gin Asn Val Thr Phe Val Asn Gin Gly Gly Trp Met Leu Ser Arg Ala 165 170 175 Ser Ala Met Glu Leu Leu Gin Ala Ala Gly Xaa 180 185 (2) INFORMATION FOR SEQ ID NO:64: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 148 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (DJ TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID N0:64: Asp Glu Val Thr Val Glu Thr Thr Ser Val Phe Arg Ala Asp Phe Leu 1 5 10 15 Ser Glu Leu Asp Ala Pro Ala Gin Ala Gly Thr Glu Ser Ala Val Ser 20 25 30 Gly Val Glu Gly Leu Pro Pro Gly Ser Ala Leu Leu Val Val Lys Arg 35 40 45 Gly Pro Asn Ala Gly Ser Arg Phe Leu Leu Asp Gin Ala Ile Thr Ser 50 55 60 Ala Gly Arg His Pro Asp Ser Asp Ile Phe Leu Asp Asp Val Thr Val 65 70 75 80 Ser Arg Arg His Ala Glu Phe Arg Leu Glu Asn Asn Glu Phe Asn Val 85 90 95 Val Asp Val Gly Ser Leu Asn Gly Thr Tyr Val Asn Arg Glu Pro Val 100 105 110 Asp Ser Ala Val Leu Ala Asn Gly Asp Glu Val Gin He Gly Lys Leu 115 120 125 Arg Leu Val Phe Leu Thr Gly Pro Lys Gin Gly Glu Asp Asp Gly Ser 130 135 140 Thr Gly Gly Pro 145 (2) INFORMATION FOR SEQ ID NO:65: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 230 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID NO:65: Thr Ser Asn Arg Pro Ala Arg Arg Gly Arg Arg Ala Pro Arg Asp Thr 1 5 10 15 Gly Pro Asp Arg Ser Ala Ser Leu Ser Leu Val Arg His Arg Arg Gin 20 25 30 Gin Arg Asp Ala Leu Cys Leu Ser Ser Thr Gin Ile Ser Arg Gin Ser 35 40 45 Asn Leu Pro Pro Ala Ala Gly Gly Ala Ala Asn Tyr Ser Arg Arg Asn 50 55 60 Phe Asp Val Arg Ile Lys Ile Phe Met Leu Val Thr Ala Val Val Leu 65 70 75 80 Leu Cys Cys Ser Gly Val Ala Thr Ala Ala Pro Lys Thr Tyr Cys Glu 85 90 95 Glu Leu Lys Gly Thr Asp Thr Gly Gin Ala Cys Gin Ile Gin Met Ser 100 105 110 Asp Pro Ala Tyr Asn He Asn He Ser Leu Pro Ser Tyr Tyr Pro Asp 115 120 125 Gin Lys Ser Leu Glu Asn Tyr Ile Ala Gin Thr Arg Asp Lys Phe Leu 130 135 140 Ser Ala Ala Thr Ser Ser Thr Pro Arg Glu Ala Pro Tyr Glu Leu Asn 145 150 155 160 Ile Thr Ser Ala Thr Tyr Gin Ser Ala Ile Pro Pro Arg Gly Thr Gin 165 170 175 Ala Val Val Leu Xaa Val Tyr His Asn Ala Gly Gly Thr His Pro Thr 180 185 190 96 Thr Thr Tyr Lys Ala Phe Asp Trp Asp Gin Ala Tyr Arg Lys Pro Ile 195 200 205 Thr Tyr " Asp Thr Leu Trp Gin Ala Asp Thr Asp Pro Leu Pro Val Val 210 215 220 Phe Pro He Val Ala Arg 225 230 (2) INFORMATION FOR SEQ ID NO:66: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 132 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID N0:66: Thr Ala Ala Ser Asp Asn Phe Gin Leu Ser Gin Gly Gly Gin Gly Phe 1 5 10 15 Ala He Pro Ile Gly Gin Ala Met Ala He Ala Gly Gin He Arg Ser 20 25 30 Gly Gly Gly Ser Pro Thr Val His He Gly Pro Thr Ala Phe Leu Gly 35 40 45 Leu Gly Val Val Asp Asn Asn Gly Asn Gly Ala Arg Val Gin Arg Val 50 55 60 Val Gly Ser Ala Pro Ala Ala Ser Leu Gly He Ser Thr Gly Asp Val 65 70 75 80 He Thr Ala Val Asp Gly Ala Pro Ile Asn Ser Ala Thr Ala Met Ala 85 90 95 Asp Ala Leu Asn Gly His His Pro Gly Asp Val Ile Ser Val Asn Trp 100 105 110 Gin Thr Lys Ser Gly Gly Thr Arg Thr Gly Asn Val Thr Leu Ala Glu 115 120 125 Gly Pro Pro Ala 130 " (2) INFORMATION FOR SEQ ID NO:67: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 100 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID N0:67: Val Pro Leu Arg Ser Pro Ser Met Ser Pro Ser Lys Cys Leu Ala Ala 1 5 10 15 Ala Gin Arg Asn Pro Val Ile Arg Arg Arg Arg Leu Ser Asn Pro Pro 20 25 30 Pro Arg Lys Tyr Arg Ser Met Pro Ser Pro Ala Thr Ala Ser Ala Gly 35 40 45 Met Ala Arg Val Arg Arg Arg Ala He Trp Arg Gly Pro Ala Thr Xaa 50 55 60 Ser Ala Gly Met Ala Arg Val Arg Arg Trp Xaa Val Met Pro Xaa Val 65 70 75 80 He Gin Ser Thr Xaa Ile Arg Xaa Xaa Gly Pro Phe Asp Asn Arg Gly 85 90 95 Ser Glu Arg Lys 100 (2) INFORMATION FOR SEQ ID NO:68: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 163 amino acids (B) TYPE: amino acid (0 STRANDEDNESS: single (DJ TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID N0:68: Met Thr Asp Asp Ile Leu Leu He Asp Thr Asp Glu Arg Val Arg Thr 1 5 10 15 Leu Thr Leu Asn Arg Pro Gin Ser Arg Asn Ala Leu Ser Ala Ala Leu 20 25 30 Arg Asp Arg Phe Phe Ala Xaa Leu Xaa Asp Ala Glu Xaa Asp Asp Asp 35 40 45 Ile Asp Val Val He Leu Thr Gly Ala Asp Pro Val Phe Cys Ala Gly 50 55 60 Leu Asp Leu Lys Val Ala Gly Arg Ala Asp Arg Ala Ala Gly His Leu 65 70 75 80 Thr Ala Val Gly Gly His Asp Gin Ala Gly Asp Arg Arg Asp Gin Arg 85 90 95 Arg Arg Gly His Arg Arg Ala Arg Thr Gly Ala Val Leu Arg His Pro 100 105 110 Asp Arg Leu Arg Ala Arg Pro Leu Arg Arg His Pro Arg Pro Gly Gly 115 120 125 Ala Ala Ala His Leu Gly Thr Gin Cys Val Leu Ala Ala Lys Gly Arg 130 135 140 His Arg Xaa Gly Pro Val Asp Glu Pro Asp Arg Arg Leu Pro Val Arg 145 150 155 160 Asp Arg Arg (2) INFORMATION FOR SEQ ID NO:69: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 344 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID N0:69: Met Lys Phe Val Asn His Ile Glu Pro Val Ala Pro Arg Arg Ala Gly 1 5 10 15 Gly Ala Val Ala Glu Val Tyr Ala Glu Ala Arg Arg Glu Phe Gly Arg 20 25 30 Leu Pro Glu Pro Leu Ala Met Leu Ser Pro Asp Glu Gly Leu Leu Thr 35 40 45 Ala Gly Trp Ala Thr Leu Arg Glu Thr Leu Leu Val Gly Gin Val Pro 50 55 60 Arg Gly Arg Lys Glu Ala Val Ala Ala Ala Val Ala Ala Ser Leu Arg 65 70 75 80 Cys Pro Trp Cys Val Asp Ala His Thr Thr Met Leu Tyr Ala Ala Gly 85 90 95 Gin Thr Asp Thr Ala Ala Ala He Leu Ala Gly Thr Ala Pro Ala Ala 100 105 110 Gly Asp Pro Asn Ala Pro Tyr Val Ala Trp Ala Ala Gly Thr Gly Thr 115 120 125 Pro Ala Gly Pro Pro Ala Pro Phe Gly Pro Asp Val Ala Ala Glu Tyr 130 135 140 Leu Gly Thr Ala Val Gin Phe His Phe Ile Ala Arg Leu Val Leu Val 145 150 155 160 Leu Leu Asp Glu Thr Phe Leu Pro Gly Gly Pro Arg Ala Gin Gin Leu 165 170 175 100 Met Arg Arg Ala Gly Gly Leu Val Phe Ala Arg Lys Val Arg Ala Glu 180 185 190 His Arg Pro Gly Arg Ser Thr Arg Arg Leu Glu Pro Arg Thr Leu Pro 195 200 205 Asp Asp Leu Ala Trp Ala Thr Pro Ser Glu Pro He Ala Thr Ala Phe 210 215 220 Ala Ala Leu Ser His His Leu Asp Thr Ala Pro His Leu Pro Pro Pro 225 230 235 240 Thr Arg Gin Val Val Arg Arg Val Val Gly Ser Trp His Gly Glu Pro 245 250 255 Met Pro Met Ser Ser Arg Trp Thr Asn Glu His Thr Ala Glu Leu Pro 260 265 270 Ala Asp Leu His Ala Pro Thr Arg Leu Ala Leu Leu Thr Gly Leu Ala 275 280 285 Pro His Gin Val Thr Asp Asp Asp Val Ala Ala Ala Arg Ser Leu Leu 290 295 300 Asp Thr Asp Ala Ala Leu Val Gly Ala Leu Ala Trp Ala Ala Phe Thr 305 310 315 320 Ala Ala Arg Arg He Gly Thr Trp Ile Gly Ala Ala Ala Glu Gly Gin 325 330 335 Val Ser Arg Gin Asn Pro Thr Gly 340 (2) INFORMATION FOR SEQ ID N0:70: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 485 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear , „,.,„ PCT US96/14674 97/09428 101 (xi) SEQUENCE DESCRIPTION: SEQ ID N0:70: Asp Asp Pro Asp Met Pro Gly Thr Val Ala Lys Ala Val Ala Asp Ala 1 ~ 5 10 15 Leu Gly Arg Gly Ile Ala Pro Val Glu Asp He Gin Asp Cys Val Glu 20 25 30 Ala Arg Leu Gly Glu Ala Gly Leu Asp Asp Val Ala Arg Val Tγr Ile 35 40 45 He Tyr Arg Gin Arg Arg Ala Glu Leu Arg Thr Ala Lys Ala Leu Leu 50 55 60 Gly Val Arg Asp Glu Leu Lys Leu Ser Leu Ala Ala Val Thr Val Leu 65 70 75 80 Arg Glu Arg Tyr Leu Leu His Asp Glu Gin Gly Arg Pro Ala Glu Ser 85 90 95 Thr Gly Glu Leu Met Asp Arg Ser Ala Arg Cys Val Ala Ala Ala Glu 100 105 110 Asp Gin Tyr Glu Pro Gly Ser Ser Arg Arg Trp Ala Glu Arg Phe Ala 115 120 125 Thr Leu Leu Arg Asn Leu Glu Phe Leu Pro Asn Ser Pro Thr Leu Met 130 135 140 Asn Ser Gly Thr Asp Leu Gly Leu Leu Ala Gly Cys Phe Val Leu Pro 145 150 155 160 He Glu Asp Ser Leu Gin Ser Ile Phe Ala Thr Leu Gly Gin Ala Ala 165 170 175 Glu Leu Gin Arg Ala Gly Gly Gly Thr Gly Tyr Ala Phe Ser His Leu 180 185 190 Arg Pro Ala Gly Asp Arg Val Ala Ser Thr Gly Gly Thr Ala Ser Gly 195 200 205 Pro Val Ser Phe Leu Arg Leu Tyr Asp Ser Ala Ala Gly Val Val Ser 210 215 220 97/09428 102 Met Gly Gly Arg Arg Arg Gly Ala Cys Met Ala Val Leu Asp Val Ser 225 230 235 240 His Pro Asp Ile Cys Asp Phe Val Thr Ala Lys Ala Glu Ser Pro Ser 245 250 255 Glu Leu Pro His Phe Asn Leu Ser Val Gly Val Thr Asp Ala Phe Leu 260 265 270 Arg Ala Val Glu Arg Asn Gly Leu His Arg Leu Val Asn Pro Arg Thr 275 280 285 Gly Lys Ile Val Ala Arg Met Pro Ala Ala Glu Leu Phe Asp Ala He 290 295 300 Cys Lys Ala Ala His Ala Gly Gly Asp Pro Gly Leu Val Phe Leu Asp 305 310 315 320 Thr Ile Asn Arg Ala Asn Pro Val Pro Gly Arg Gly Arg Ile Glu Ala 325 330 335 Thr Asn Pro Cys Gly Glu Val Pro Leu Leu Pro Tyr Glu Ser Cys Asn 340 345 350 Leu Gly Ser Ile Asn Leu Ala Arg Met Leu Ala Asp Gly Arg Val Asp 355 360 365 Trp Asp Arg Leu Glu Glu Val Ala Gly Val Ala Val Arg Phe Leu Asp 370 375 380 Asp Val He Asp Val Ser Arg Tyr Pro Phe Pro Glu Leu Gly Glu Ala 385 390 395 400 Ala Arg Ala Thr Arg Lys He Gly Leu Gly Val Met Gly Leu Ala Glu 405 410 415 Leu Leu Ala Ala Leu Gly Ile Pro Tyr Asp Ser Glu Glu Ala Val Arg 420 425 430 Leu Ala Thr Arg Leu Met Arg Arg Ile Gin Gin Ala Ala His Thr Ala 435 440 445 Ser Arg Arg Leu Ala Glu Glu Arg Gly Ala Phe Pro Ala Phe Thr Asp 450 455 460 Ser Arg Phe Ala Arg Ser Gly Pro Arg Arg Asn Ala Gin Val Thr Ser 465 470 475 480 Val Ala Pro Thr Gly 485 (2) INFORMATION FOR SEQ ID NO:71: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 267 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID NO:71: Gly Val He Val Leu Asp Leu Glu Pro Arg Gly Pro Leu Pro Thr Glu 1 5 10 15 Ile Tyr Trp Arg Arg Arg Gly Leu Ala Leu Gly Ile Ala Val Val Val 20 25 30 Val Gly Ile Ala Val Ala He Val Ile Ala Phe Val Asp Ser Ser Ala 35 40 45 Gly Ala Lys Pro Val Ser Ala Asp Lys Pro Ala Ser Ala Gin Ser His 50 55 60 Pro Gly Ser Pro Ala Pro Gin Ala Pro Gin Pro Ala Gly Gin Thr Glu 65 70 75 80 Gly Asn Ala Ala Ala Ala Pro Pro Gin Gly Gin Asn Pro Glu Thr Pro 85 90 95 Thr Pro Thr Ala Ala Val Gin Pro Pro Pro Val Leu Lys Glu Gly Asp 100 105 110 Asp Cys Pro Asp Ser Thr Leu Ala Val Lys Gly Leu Thr Asn Ala Pro 115 120 125 Gin Tyr Tyr Val Gly Asp Gin Pro Lys Phe Thr Met Val Val Thr Asn 130 135 140 He Gly Leu Val Ser Cys Lys Arg Asp Val Gly Ala Ala Val Leu Ala 145 _ 150 155 160 Ala Tyr Val Tyr Ser Leu Asp Asn Lys Arg Leu Trp Ser Asn Leu Asp 165 170 175 Cys Ala Pro Ser Asn Glu Thr Leu Val Lys Thr Phe Ser Pro Gly Glu 180 185 190 Gin Val Thr Thr Ala Val Thr Trp Thr Gly Met Gly Ser Ala Pro Arg 195 200 205 Cys Pro Leu Pro Arg Pro Ala Ile Gly Pro Gly Thr Tyr Asn Leu Val 210 215 220 Val Gin Leu Gly Asn Leu Arg Ser Leu Pro Val Pro Phe He Leu Asn 225 230 235 240 Gin Pro Pro Pro Pro Pro Gly Pro Val Pro Ala Pro Gly Pro Ala Gin 245 250 255 Ala Pro Pro Pro Glu Ser Pro Ala Gin Gly Gly 260 265 (2) INFORMATION FOR SEQ ID NO:72: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 97 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (xi ) SEQUENCE DESCRIPTION : SEQ ID NO: 72: Leu He Ser Thr Gly Lys Al a Ser Hi s Ala Ser Leu Gly Val Gi n Val 1 5 10 15 Thr Asn Asp Lys Asp Thr Pro Gly Al a Lys He Val Gl u Val Val Al a 20 25 30 Gly Gly Ala Ala Ala Asn Ala Gly Val Pro Lys Gly Val Val Val Thr 35 40 45 Lys Vaf Asp Asp Arg Pro He Asn Ser Ala Asp Ala Leu Val Ala Ala 50 55 60 Val Arg Ser Lys Ala Pro Gly Ala Thr Val Ala Leu Thr Phe Gin Asp 65 70 75 80 Pro Ser Gly Gly Ser Arg Thr Val Gin Val Thr Leu Gly Lys Ala Glu 85 90 95 Gin (2) INFORMATION FOR SEQ ID NO:73: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 364 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID NO:73: Gly Ala Ala Val Ser Leu Leu Ala Ala Gly Thr Leu Val Leu Thr Ala 1 5 10 15 Cys Gly Gly Gly Thr Asn Ser Ser Ser Ser Gly Ala Gly Gly Thr Ser 20 25 30 Gly Ser Val His Cys Gly Gly Lys Lys Glu Leu His Ser Ser Gly Ser 35 40 45 Thr Ala Gin Glu Asn Ala Met Glu Gin Phe Val Tyr Ala Tyr Val Arg 50 55 60 Ser Cys Pro Gly Tyr Thr Leu Asp Tyr Asn Ala Asn Gly Ser Gly Ala 65 70 75 80 Gly Val Thr Gin Phe Leu Asn Asn Glu Thr Asp Phe Ala Gly Ser Asp 85 90 95 Val Pro Leu Asn Pro Ser Thr Gly Gin Pro Asp Arg Ser Ala Glu Arg 100 105 110 Cys Gly Ser Pro Ala Trp Asp Leu Pro Thr Val Phe Gly Pro Ile Ala 115 120 125 Ile Thr Tyr Asn He Lys Gly Val Ser Thr Leu Asn Leu Asp Gly Pro 130 135 140 Thr Thr Ala Lys He Phe Asn Gly Thr Ile Thr Val Trp Asn Asp Pro 145 150 155 160 Gin He Gin Ala Leu Asn Ser Gly Thr Asp Leu Pro Pro Thr Pro Ile 165 170 175 Ser Val He Phe Arg Ser Asp Lys Ser Gly Thr Ser Asp Asn Phe Gin 180 185 190 Lys Tyr Leu Asp Gly Val Ser Asn Gly Ala Trp Gly Lys Gly Ala Ser 195 200 205 Glu Thr Phe Ser Gly Gly Val Gly Val Gly Ala Ser Gly Asn Asn Gly 210 215 220 Thr Ser Ala Leu Leu Gin Thr Thr Asp Gly Ser Ile Thr Tyr Asn Glu 225 230 235 240 Trp Ser Phe Ala Val Gly Lys Gin Leu Asn Met Ala Gin Ile Ile Thr 245 250 255 Ser Ala Gly Pro Asp Pro Val Ala He Thr Thr Glu Ser Val Gly Lys 260 265 270 Thr Ile Ala Gly Ala Lys He Met Gly Gin Gly Asn Asp Leu Val Leu 275 280 285 Asp Thr Ser Ser Phe Tyr Arg Pro Thr Gin Pro Gly Ser Tyr Pro He 290 295 300 Val Leu Ala Thr Tyr Glu He Val Cys Ser Lys Tyr Pro Asp Ala Thr 305 310 315 320 Thr Gly Thr Ala Val Arg Ala Phe Met Gin Ala Ala Ile Gly Pro Gly 325 330 335 Gin Glu Gly Leu Asp Gin Tyr Gly Ser Ile Pro Leu Pro Lys Ser Phe 340 345 350 Gin Ala Lys Leu Ala Ala Ala Val Asn Ala He Ser 355 360 (2) INFORMATION FOR SEQ ID NO:74: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 309 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID NO:74: Gin Ala Ala Ala Gly Arg Ala Val Arg Arg Thr Gly His Ala Glu Asp 1 5 10 15 Gin Thr His Gin Asp Arg Leu His His Gly Cys Arg Arg Ala Ala Val 20 25 30 Val Val Arg Gin Asp Arg Ala Ser Val Ser Ala Thr Ser Ala Arg Pro 35 40 45 Pro Arg Arg His Pro Ala Gin Gly His Arg Arg Arg Val Ala Pro Ser 50 55 60 Gly Gly Arg Arg Arg Pro His Pro His His Val Gin Pro Asp Asp Arg 65 70 75 80 Arg Asp Arg Pro Ala Leu Leu Asp Arg Thr Gin Pro Ala Glu His Pro 85 90 95 Asp Pro His Arg Arg Gly Pro Ala Asp Pro Gly Arg Val Arg Gly Arg 100 105 110 Gly Arg Leu Arg Arg Val Asp Asp Gly Arg Leu Gin Pro Asp Arg Asp 108 115 120 125 Ala Asp His Gly Ala Pro Val Arg Gly Arg Gly Pro His Arg Gly Val 130 135 140 Gin His Arg Gly Gly Pro Val Phe Val Arg Arg Val Pro Gly Val Arg 145 150 155 160 Cys Ala His Arg Arg Gly His Arg Arg Val Ala Ala Pro Gly Gin Gly 165 170 175 Asp Val Leu Arg Ala Gly Leu Arg Val Glu Arg Leu Arg Pro Val Ala 180 185 190 Ala Val Glu Asn Leu His Arg Gly Ser Gin Arg Ala Asp Gly Arg Val 195 200 205 Phe Arg Pro He Arg Arg Gly Ala Arg Leu Pro Ala Arg Arg Ser Arg 210 215 220 Ala Gly Pro Gin Gly Arg Leu His Leu Asp Gly Ala Gly Pro Ser Pro 225 230 235 240 Leu Pro Ala Arg Ala Gly Gin Gin Gin Pro Ser Ser Ala Gly Gly Arg 245 250 255 Arg Ala Gly Gly Ala Glu Arg Ala Asp Pro Gly Gin Arg Gly Arg His 260 265 270 His Gin Gly Gly His Asp Pro Gly Arg Gin Gly Ala Gin Arg Gly Thr 275 280 285 Ala Gly Val Ala His Ala Ala Ala Gly Pro Arg Arg Ala Ala Val Arg 290 295 300 Asn Arg Pro Arg Arg 305 (2) INFORMATION FOR SEQ ID N0:75: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 580 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID N0:75: Ser Ala Val Trp Cys Leu Asn Gly Phe Thr Gly Arg His Arg His Gly 1 5 10 15 Arg Cys Arg Val Arg Ala Ser Gly Trp Arg Ser Ser Asn Arg Trp Cys 20 25 30 Ser Thr Thr Ala Asp Cys Cys Ala Ser Lys Thr Pro Thr Gin Ala Ala 35 40 45 Ser Pro Leu Glu Arg Arg Phe Thr Cys Cys Ser Pro Ala Val Gly Cys 50 55 60 Arg Phe Arg Ser Phe Pro Val Arg Arg Leu Ala Leu Gly Ala Arg Thr 65 70 75 80 Ser Arg Thr Leu Gly Val Arg Arg Thr Leu Ser Gin Trp Asn Leu Ser 85 90 95 Pro Arg Ala Gin Pro Ser Cys Ala Val Thr Val Glu Ser His Thr His 100 105 110 Ala Ser Pro Arg Met Ala Lys Leu Ala Arg Val Val Gly Leu Val Gin 115 120 125 Glu Glu Gin Pro Ser Asp Met Thr Asn His Pro Arg Tyr Ser Pro Pro 130 135 140 Pro Gin Gin Pro Gly Thr Pro Gly Tyr Ala Gin Gly Gin Gin Gin Thr 145 150 155 160 Tyr Ser Gin Gin Phe Asp Trp Arg Tyr Pro Pro Ser Pro Pro Pro Gin 165 170 175 Pro Thr Gin Tyr Arg Gin Pro Tyr Glu Ala Leu Gly Gly Thr Arg Pro 180 185 190 Gly Leu He Pro Gly Val He Pro Thr Met Thr Pro Pro Pro Gly Met 195 200 205 „„.„„ PCT/US96/14674 97/09428 110 Val Arg Gin Arg Pro Arg Ala Gly Met Leu Ala He Gly Ala Val Thr 210 215 220 He Ala " Val Val Ser Ala Gly Ile Gly Gly Ala Ala Ala Ser Leu Val 225 230 235 240 Gly Phe Asn Arg Ala Pro Ala Gly Pro Ser Gly Gly Pro Val Ala Ala 245 250 255 Ser Ala Ala Pro Ser He Pro Ala Ala Asn Met Pro Pro Gly Ser Val 260 265 270 Glu Gin Val Ala Ala Lys Val Val Pro Ser Val Val Met Leu Glu Thr 275 280 285 Asp Leu Gly Arg Gin Ser Glu Glu Gly Ser Gly Ile Ile Leu Ser Ala 290 295 300 Glu Gly Leu He Leu Thr Asn Asn His Val He Ala Ala Ala Ala Lys 305 310 315 320 Pro Pro Leu Gly Ser Pro Pro Pro Lys Thr Thr Val Thr Phe Ser Asp 325 330 335 Gly Arg Thr Ala Pro Phe Thr Val Val Gly Ala Asp Pro Thr Ser Asp 340 345 350 He Ala Val Val Arg Val Gin Gly Val Ser Gly Leu Thr Pro He Ser 355 360 365 Leu Gly Ser Ser Ser Asp Leu Arg Val Gly Gin Pro Val Leu Ala Ile 370 375 380 Gly Ser Pro Leu Gly Leu Glu Gly Thr Val Thr Thr Gly Ile Val Ser 385 390 395 400 Ala Leu Asn Arg Pro Val Ser Thr Thr Gly Glu Ala Gly Asn Gin Asn 405 410 415 Thr Val Leu Asp Ala Ile Gin Thr Asp Ala Ala He Asn Pro Gly Asn 420 425 430 Ser Gly Gly Ala Leu Val Asn Met Asn Ala Gin Leu Val Gly Val Asn 435 440 445 Ser Ala Ile Ala Thr Leu Gly Ala Asp Ser Ala Asp Ala Gin Ser Gly 450 455 460 Ser He Gly Leu Gly Phe Ala Ile Pro Val Asp Gin Ala Lys Arg He 465 470 475 480 Ala Asp Glu Leu Ile Ser Thr Gly Lys Ala Ser His Ala Ser Leu Gly 485 490 495 Val Gin Val Thr Asn Asp Lys Asp Thr Pro Gly Ala Lys He Val Glu 500 505 510 Val Val Ala Gly Gly Ala Ala Ala Asn Ala Gly Val Pro Lys Gly Val 515 520 525 Val Val Thr Lys Val Asp Asp Arg Pro Ile Asn Ser Ala Asp Ala Leu 530 535 540 Val Ala Ala Val Arg Ser Lys Ala Pro Gly Ala Thr Val Ala Leu Thr 545 550 555 560 Phe Gin Asp Pro Ser Gly Gly Ser Arg Thr Val Gin Val Thr Leu Gly 565 570 575 Lys Ala Glu Gin 580 (2) INFORMATION FOR SEQ ID NO:76: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 233 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID NO:76: Met Asn Asp Gly Lys Arg Ala Val Thr Ser Ala Val Leu Val Val Leu 1 5 10 15 Gly Ala Cys Leu Ala Leu Trp Leu Ser Gly Cys Ser Ser Pro Lys Pro 20 25 30 Asp Ala Glu Glu Gin Gly Val Pro Val Ser Pro Thr Ala Ser Asp Pro "" 35 40 45 Ala Leu Leu Ala Glu Ile Arg Gin Ser Leu Asp Ala Thr Lys Gly Leu 50 55 60 Thr Ser Val His Val Ala Val Arg Thr Thr Gly Lys Val Asp Ser Leu 65 70 75 80 Leu Gly He Thr Ser Ala Asp Val Asp Val Arg Ala Asn Pro Leu Ala 85 90 95 Ala Lys Gly Val Cys Thr Tyr Asn Asp Glu Gin Gly Val Pro Phe Arg 100 105 110 Val Gin Gly Asp Asn Ile Ser Val Lys Leu Phe Asp Asp Trp Ser Asn 115 120 125 Leu Gly Ser Ile Ser Glu Leu Ser Thr Ser Arg Val Leu Asp Pro Ala 130 135 140 Ala Gly Val Thr Gin Leu Leu Ser Gly Val Thr Asn Leu Gin Ala Gin 145 150 155 160 Gly Thr Glu Val He Asp Gly Ile Ser Thr Thr Lys Ile Thr Gly Thr 165 170 175 Ile Pro Ala Ser Ser Val Lys Met Leu Asp Pro Gly Ala Lys Ser Ala 180 185 190 Arg Pro Ala Thr Val Trp Ile Ala Gin Asp Gly Ser His His Leu Val 195 200 205 Arg Ala Ser Ile Asp Leu Gly Ser Gly Ser Ile Gin Leu Thr Gin Ser 210 215 220 Lys Trp Asn Glu Pro Val Asn Val Asp 225 230 (2) INFORMATION FOR SEQ ID NO:77: (i) SEQUENCE CHARACTERISTICS: 113 (A) LENGTH: 66 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (xi ) SEQUENCE DESCRIPTION: SEQ ID NO: 77: Val He Asp He He Gly Thr Ser Pro Thr Ser Trp Glu Gin Ala Ala 1 5 10 15 Ala Glu Ala Val Gin Arg Ala Arg Asp Ser Val Asp Asp He Arg Val 20 25 30 Ala Arg Val Ile Glu Gin Asp Met Ala Val Asp Ser Ala Gly Lys He 35 40 45 Thr Tyr Arg He Lys Leu Glu Val Ser Phe Lys Met Arg Pro Ala Gin 50 55 60 Pro Arg 65 (2) INFORMATION FOR SEQ ID NO:78: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 69 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (xi ) SEQUENCE DESCRIPTION: SEQ ID N0:78: Val Pro Pro Ala Pro Pro Leu Pro Pro Leu Pro Pro Ser Pro He Ser 1 5 10 15 Cys Ala Ser Pro Pro Ser Pro Pro Leu Pro Pro Ala Pro Pro Val Ala 20 25 30 114 Pro Gly Pro Pro Met Pro Pro Leu Asp Pro Trp Pro Pro Ala Pro Pro 35 40 45 Leu Pro Tyr Ser Thr Pro Pro Gly Ala Pro Leu Pro Pro Ser Pro Pro 50 55 60 Ser Pro Pro Leu Pro 65 (2) INFORMATION FOR SEQ ID NO:79: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 355 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID N0:79: Met Ser Asn Ser Arg Arg Arg Ser Leu Arg Trp Ser Trp Leu Leu Ser 1 5 10 15 Val Leu Ala Ala Val Gly Leu Gly Leu Ala Thr Ala Pro Ala Gin Ala 20 25 30 Ala Pro Pro Ala Leu Ser Gin Asp Arg Phe Ala Asp Phe Pro Ala Leu 35 40 45 Pro Leu Asp Pro Ser Ala Met Val Ala Gin Val Ala Pro Gin Val Val 50 55 60 Asn Ile Asn Thr Lys Leu Gly Tyr Asn Asn Ala Val Gly Ala Gly Thr 65 70 75 80 Gly Ile Val Ile Asp Pro Asn Gly Val Val Leu Thr Asn Asn His Val 85 90 95 Ile Ala Gly Ala Thr Asp Ile Asn Ala Phe Ser Val Gly Ser Gly Gin 100 105 110 Thr Tyr Gly Val Asp Val Val Gly Tyr Asp Arg Thr Gin Asp Val Ala 115 120 125 Val Leu Gin Leu Arg Gly Ala Gly Gly Leu Pro Ser Ala Ala Ile Gly 130 " 135 140 Gly Gly Val Ala Val Gly Glu Pro Val Val Ala Met Gly Asn Ser Gly 145 150 155 160 Gly Gin Gly Gly Thr Pro Arg Ala Val Pro Gly Arg Val Val Ala Leu 165 170 175 Gly Gin Thr Val Gin Ala Ser Asp Ser Leu Thr Gly Ala Glu Glu Thr 180 185 190 Leu Asn Gly Leu Ile Gin Phe Asp Ala Ala Ile Gin Pro Gly Asp Ser 195 200 205 Gly Gly Pro Val Val Asn Gly Leu Gly Gin Val Val Gly Met Asn Thr 210 215 220 Ala Ala Ser Asp Asn Phe Gin Leu Ser Gin Gly Gly Gin Gly Phe Ala 225 230 235 240 Ile Pro Ile Gly Gin Ala Met Ala Ile Ala Gly Gin He Arg Ser Gly 245 250 255 Gly Gly Ser Pro Thr Val His Ile Gly Pro Thr Ala Phe Leu Gly Leu 260 265 270 Gly Val Val Asp Asn Asn Gly Asn Gly Ala Arg Val Gin Arg Val Val 275 280 285 Gly Ser Ala Pro Ala Ala Ser Leu Gly lie Ser Thr Gly Asp Val He 290 295 300 Thr Ala Val Asp Gly Ala Pro Ile Asn Ser Ala Thr Ala Met Ala Asp 305 310 315 320 Ala Leu Asn Gly His His Pro Gly Asp Val Ile Ser Val Asn Trp Gin 325 330 335 Thr Lys Ser Gly Gly Thr Arg Thr Gly Asn Val Thr Leu Ala Glu Gly 340 345 350 116 Pro Pro Ala 355 (2) INFORMATION FOR SEQ ID NO:80: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 205 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID N0:80: Ser Pro Lys Pro Asp Ala Glu Glu Gin Gly Val Pro Val Ser Pro Thr 1 5 10 15 Ala Ser Asp Pro Ala Leu Leu Ala Glu Ile Arg Gin Ser Leu Asp Ala 20 25 30 Thr Lys Gly Leu Thr Ser Val His Val Ala Val Arg Thr Thr Gly Lys 35 40 45 Val Asp Ser Leu Leu Gly Ile Thr Ser Ala Asp Val Asp Val Arg Ala 50 55 60 Asn Pro Leu Ala Ala Lys Gly Val Cys Thr Tyr Asn Asp Glu Gin Gly 65 70 75 80 Val Pro Phe Arg Val Gin Gly Asp Asn He Ser Val Lys Leu Phe Asp 85 90 95 Asp Trp Ser Asn Leu Gly Ser He Ser Glu Leu Ser Thr Ser Arg Val 100 105 110 Leu Asp Pro Ala Ala Gly Val Thr Gin Leu Leu Ser Gly Val Thr Asn 115 120 125 Leu Gin Ala Gin Gly Thr Glu Val He Asp Gly He Ser Thr Thr Lys 130 135 140 He Thr Gly Thr He Pro Ala Ser Ser Val Lys Met Leu Asp Pro Gly 145 150 155 160 Ala Lys Ser Ala Arg Pro Ala Thr Val Trp Ile Ala Gin Asp Gly Ser 165 170 175 His His Leu Val Arg Ala Ser Ile Asp Leu Gly Ser Gly Ser He Gin 180 185 190 Leu Thr Gin Ser Lys Trp Asn Glu Pro Val Asn Val Asp 195 200 205 (2) INFORMATION FOR SEQ ID NO:81: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 286 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (xi ) SEQUENCE DESCRIPTION: SEQ ID N0:81 : Gly Asp Ser Phe Trp Ala Ala Ala Asp Gin Met Ala Arg Gly Phe Val 1 5 10 15 Leu Gly Ala Thr Ala Gly Arg Thr Thr Leu Thr Gly Glu Gly Leu Gin 20 25 30 His Ala Asp Gly His Ser Leu Leu Leu Asp Ala Thr Asn Pro Al a Val 35 40 45 Val Al a Tyr Asp Pro Al a Phe Ala Tyr Glu Ile Gly Tyr Ile Xaa Glu 50 55 60 Ser Gly Leu Ala Arg Met Cys Gly Glu Asn Pro Glu Asn Ile Phe Phe 65 70 75 80 Tyr Ile Thr Val Tyr Asn Glu Pro Tyr Val Gin Pro Pro Glu Pro Glu 85 90 95 Asn Phe Asp Pro Gl u Gly Val Leu Gly Gly Ile Tyr Arg Tyr His Al a 100 105 110 Ala Thr Glu Gin Arg Thr Asn Lys Xaa Gin He Leu Ala Ser Gly Val 115 120 125 Ala Met Pro Ala Ala Leu Arg Ala Ala Gin Met Leu Ala Ala Glu Trp 130 135 140 Asp Val Ala Ala Asp Val Trp Ser Val Thr Ser Trp Gly Glu Leu Asn 145 150 155 160 Arg Asp Gly Val Val Ile Glu Thr Glu Lys Leu Arg His Pro Asp Arg 165 170 175 Pro Ala Gly Val Pro Tyr Val Thr Arg Ala Leu Glu Asn Ala Arg Gly 180 185 190 Pro Val Ile Ala Val Ser Asp Trp Met Arg Ala Val Pro Glu Gin Ile 195 200 205 Arg Pro Trp Val Pro Gly Thr Tyr Leu Thr Leu Gly Thr Asp Gly Phe 210 215 220 Gly Phe Ser Asp Thr Arg Pro Ala Gly Arg Arg Tyr Phe Asn Thr Asp 225 230 235 240 Ala Glu Ser Gin Val Gly Arg Gly Phe Gly Arg Gly Trp Pro Gly Arg 245 250 255 Arg Val Asn He Asp Pro Phe Gly Ala Gly Arg Gly Pro Pro Ala Gin 260 265 270 Leu Pro Gly Phe Asp Glu Gly Gly Gly Leu Arg Pro Xaa Lys 275 280 285 (2) INFORMATION FOR SEQ ID NO:82: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 173 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID N0:82: Thr Lys Phe His Ala Leu Met Gin Glu Gin Ile His Asn Glu Phe Thr 1 5 10 15 Ala Ala Gin Gin Tyr Val Ala Ile Ala Val Tyr Phe Asp Ser Glu Asp 20 25 30 Leu Pro Gin Leu Ala Lys His Phe Tyr Ser Gin Ala Val Glu Glu Arg 35 40 45 Asn His Ala Met Met Leu Val Gin His Leu Leu Asp Arg Asp Leu Arg 50 55 60 Val Glu He Pro Gly Val Asp Thr Val Arg Asn Gin Phe Asp Arg Pro 65 70 75 80 Arg Glu Ala Leu Ala Leu Ala Leu Asp Gin Glu Arg Thr Val Thr Asp 85 90 95 Gin Val Gly Arg Leu Thr Ala Val Ala Arg Asp Glu Gly Asp Phe Leu 100 105 110 Gly Glu Gin Phe Met Gin Trp Phe Leu Gin Glu Gin Ile Glu Glu Val 115 120 125 Ala Leu Met Ala Thr Leu Val Arg Val Ala Asp Arg Ala Gly Ala Asn 130 135 140 Leu Phe Glu Leu Glu Asn Phe Val Ala Arg Glu Val Asp Val Ala Pro 145 150 155 160 Ala Ala Ser Gly Ala Pro His Ala Ala Gly Gly Arg Leu 165 170 (2) INFORMATION FOR SEQ ID N0:83: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 107 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear 120 (xi) SEQUENCE DESCRIPTION: SEQ ID N0:83: Arg Ala Asp Glu Arg Lys Asn Thr Thr Met Lys Met Val Lys Ser He 1 5 10 15 Ala Ala Gly Leu Thr Ala Ala Ala Ala Ile Gly Ala Ala Ala Ala Gly 20 25 30 Val Thr Ser Ile Met Ala Gly Gly Pro Val Val Tyr Gin Met Gin Pro 35 40 45 Val Val Phe Gly Ala Pro Leu Pro Leu Asp Pro Xaa Ser Ala Pro Xaa 50 55 60 Val Pro Thr Ala Ala Gin Trp Thr Xaa Leu Leu Asn Xaa Leu Xaa Asp 65 70 75 80 Pro Asn Val Ser Phe Xaa Asn Lys Gly Ser Leu Val Glu Gly Gly Ile 85 90 95 Gly Gly Xaa Glu Gly Xaa Xaa Arg Arg Xaa Gin 100 105 (2) INFORMATION FOR SEQ ID NO:84: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 125 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID N0:84: Val Leu Ser Val Pro Val Gly Asp Gly Phe Trp Xaa Arg Val Val Asn 1 5 10 15 Pro Leu Gly Gin Pro Ile Asp Gly Arg Gly Asp Val Asp Ser Asp Thr 20 25 30 121 Arg Arg Ala Leu Glu Leu Gin Ala Pro Ser Val Val Xaa Arg Gin Gly 35 40 45 Val Lys Glu Pro Leu Xaa Thr Gly Ile Lys Ala Ile Asp Ala Met Thr 50 55 60 Pro Ile Gly Arg Gly Gin Arg Gin Leu Ile He Gly Asp Arg Lys Thr 65 70 75 80 Gly Lys Asn Arg Arg Leu Cys Arg Thr Pro Ser Ser Asn Gin Arg Glu 85 90 95 Glu Leu Gly Val Arg Trp Ile Pro Arg Ser Arg Cys Ala Cys Val Tyr 100 105 110 Val Gly His Arg Ala Arg Arg Gly Thr Tyr His Arg Arg 115 120 125 (2) INFORMATION FOR SEQ ID NO:85: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 117 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID NO:85: Cys Asp Ala Val Met Gly Phe Leu Gly Gly Ala Gly Pro Leu Ala Val 1 5 10 15 Val Asp Gin Gin Leu Val Thr Arg Val Pro Gin Gly Trp Ser Phe Ala 20 25 30 Gin Ala Ala Ala Val Pro Val Val Phe Leu Thr Ala Trp Tyr Gly Leu 35 40 45 Ala Asp Leu Ala Glu He Lys Ala Gly Glu Ser Val Leu Ile His Ala 50 55 60 Gly Thr Gly Gly Val Gly Met Ala Ala Val Gin Leu Ala Arg Gin Trp 122 65 70 75 80 Gly Val Glu Val Phe Val Thr Ala Ser Arg Gly Lys Trp Asp Thr Leu 85 90 95 Arg Ala Xaa Xaa Phe Asp Asp Xaa Pro Tyr Arg Xaa Phe Pro Hi s Xaa 100 105 110 Arg Ser Ser Xaa Gly 115 (2) INFORMATION FOR SEQ ID NO:86: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 103 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID N0:86: Met Tyr Arg Phe Ala Cys Arg Thr Leu Met Leu Ala Ala Cys He Leu 1 5 10 15 Ala Thr Gly Val Ala Gly Leu Gly Val Gly Ala Gin Ser Ala Ala Gin 20 25 30 Thr Ala Pro Val Pro Asp Tyr Tyr Trp Cys Pro Gly Gin Pro Phe Asp 35 40 45 Pro Ala Trp Gly Pro Asn Trp Asp Pro Tyr Thr Cys His Asp Asp Phe 50 55 60 His Arg Asp Ser Asp Gly Pro Asp His Ser Arg Asp Tyr Pro Gly Pro 65 70 75 80 He Leu Glu Gly Pro Val Leu Asp Asp Pro Gly Ala Ala Pro Pro Pro 85 90 95 Pro Ala Ala Gly Gly Gly Ala 100 123 (2) INFORMATION FOR SEQ ID NO: 87 : (i ) SEQUENCE CHARACTERISTICS : (A) LENGTH: 88 ami no acids (B) TYPE : amino aci d (C) STRANDEDNESS : single (D) TOPOLOGY: l inear (xi) SEQUENCE DESCRIPTION: SEQ ID N0:87: Val Gin Cys Arg Val Trp Leu Glu Ile Gin Trp Arg Gly Met Leu Gly 1 5 10 15 Ala Asp Gin Ala Arg Ala Gly Gly Pro Ala Arg Ile Trp Arg Glu His 20 25 30 Ser Met Ala Ala Met Lys Pro Arg Thr Gly Asp Gly Pro Leu Glu Ala 35 40 45 Thr Lys Glu Gly Arg Gly Ile Val Met Arg Val Pro Leu Glu Gly Gly 50 55 60 Gly Arg Leu Val Val Glu Leu Thr Pro Asp Glu Ala Ala Ala Leu Gly 65 70 75 80 Asp Glu Leu Lys Gly Val Thr Ser 85 (2) INFORMATION FOR SEQ ID NO:88: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 95 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID N0:88: Thr Asp Ala Ala Thr Leu Ala Gin Glu Ala Gly Asn Phe Glu Arg Ile 1 5 10 15 Ser Gly Asp Leu Lys Thr Gin He Asp Gin Val Glu Ser Thr Ala Gly 20 25 30 Ser Leu Gin Gly Gin Trp Arg Gly Ala Ala Gly Thr Ala Ala Gin Ala 35 40 45 Ala Val Val Arg Phe Gin Glu Ala Ala Asn Lys Gin Lys Gin Glu Leu 50 55 60 Asp Glu He Ser Thr Asn He Arg Gin Ala Gly Val Gin Tyr Ser Arg 65 70 75 80 Ala Asp Glu Glu Gin Gin Gin Ala Leu Ser Ser Gin Met Gly Phe 85 90 95 (2) INFORMATION FOR SEQ ID N0:89: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 166 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (xi ) SEQUENCE DESCRIPTION: SEQ ID NO:89: Met Thr Gin Ser Gin Thr Val Thr Val Asp Gin Gin Glu He Leu Asn 1 5 10 15 Arg Ala Asn Glu Val Glu Ala Pro Met Ala Asp Pro Pro Thr Asp Val 20 25 30 Pro Ile Thr Pro Cys Glu Leu Thr Xaa Xaa Lys Asn Ala Ala Gin Gin 35 40 45 Xaa Val Leu Ser Ala Asp Asn Met Arg Glu Tyr Leu Ala Ala Gly Ala 50 55 60 Lys Glu Arg Gin Arg Leu Ala Thr Ser Leu Arg Asn Ala Ala Lys Xaa 65 70 75 80 Tyr Gly Glu Val Asp Glu Glu Ala Ala Thr Ala Leu Asp Asn Asp Gly 85 90 95 Glu Gly Thr Val Gin Ala Glu Ser Ala Gly Ala Val Gly Gly Asp Ser 100 105 110 Ser Ala Glu Leu Thr Asp Thr Pro Arg Val Ala Thr Ala Gly Glu Pro 115 120 125 Asn Phe Met Asp Leu Lys Glu Ala Ala Arg Lys Leu Glu Thr Gly Asp 130 135 140 Gin Gly Ala Ser Leu Ala His Xaa Gly Asp Gly Trp Asn Thr Xaa Thr 145 150 155 160 Leu Thr Leu Gin Gly Asp 165 (2) INFORMATION FOR SEQ ID NO:90: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 5 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID N0:90: Arg Ala Glu Arg Met 1 5 (2) INFORMATION FOR SEQ ID NO:91: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 263 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single 97/09428 126 (D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID NO:91: Val Ala Trp Met Ser Val Thr Ala Gly Gin Ala Glu Leu Thr Ala Ala 1 5 10 15 Gin Val Arg Val Ala Ala Ala Ala Tyr Glu Thr Ala Tyr Gly Leu Thr 20 25 30 Val Pro Pro Pro Val Ile Ala Glu Asn Arg Ala Glu Leu Met Ile Leu 35 40 45 Ile Ala Thr Asn Leu Leu Gly Gin Asn Thr Pro Ala Ile Ala Val Asn 50 55 60 Glu Ala Glu Tyr Gly Glu Met Trp Ala Gin Asp Ala Ala Ala Met Phe 65 70 75 80 Gly Tyr Ala Ala Ala Thr Ala Thr Ala Thr Ala Thr Leu Leu Pro Phe 85 90 95 Glu Glu Ala Pro Glu Met Thr Ser Ala Gly Gly Leu Leu Glu Gin Ala 100 105 110 Ala Ala Val Glu Glu Ala Ser Asp Thr Ala Ala Ala Asn Gin Leu Met 115 120 125 Asn Asn Val Pro Gin Ala Leu Lys Gin Leu Ala Gin Pro Thr Gin Gly 130 135 140 Thr Thr Pro Ser Ser Lys Leu Gly Gly Leu Trp Lys Thr Val Ser Pro 145 150 155 160 His Arg Ser Pro Ile Ser Asn Met Val Ser Met Ala Asn Asn His Met 165 170 175 Ser Met Thr Asn Ser Gly Val Ser Met Thr Asn Thr Leu Ser Ser Met 180 185 190 Leu Lys Gly Phe Ala Pro Ala Ala Ala Ala Gin Ala Val Gin Thr Ala 195 200 205 Ala Gin Asn Gly Val Arg Ala Met Ser Ser Leu Gly Ser Ser Leu Gly 210 215 220 Ser Ser Gly Leu Gly Gly Gly Val Ala Ala Asn Leu Gly Arg Ala Ala 225 230 235 240 Ser Val Arg Tyr Gly His Arg Asp Gly Gly Lys Tyr Ala Xaa Ser Gly 245 250 255 Arg Arg Asn Gly Gly Pro Ala 260 (2) INFORMATION FOR SEQ ID NO:92: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 303 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID N0:92: Met Thr Tyr Ser Pro Gly Asn Pro Gly Tyr Pro Gin Ala Gin Pro Ala 1 5 10 15 Gly Ser Tyr Gly Gly Val Thr Pro Ser Phe Ala His Ala Asp Glu Gly 20 25 30 Ala Ser Lys Leu Pro Met Tyr Leu Asn Ile Ala Val Ala Val Leu Gly 35 40 45 Leu Ala Ala Tyr Phe Ala Ser Phe Gly Pro Met Phe Thr Leu Ser Thr 50 55 60 Glu Leu Gly GlylGly Asp Gly Ala Val Ser Gly Asp Thr Gly Leu Pro 65 70 75 80 Val Gly Val Ala Leu Leu Ala Ala Leu Leu Ala Gly Val Val Leu Val 85 90 95 128 Pro Lys Ala Lys Ser His Val Thr Val Val Ala Val Leu Gly Val Leu 100 105 110 Gly Val Phe Leu Met Val Ser Ala Thr Phe Asn Lys Pro Ser Ala Tyr 115 120 125 Ser Thr Gly Trp Ala Leu Trp Val Val Leu Ala Phe Ile Val Phe Gin 130 135 140 Ala Val Ala Ala Val Leu Ala Leu Leu Val Glu Thr Gly Ala Ile Thr 145 150 155 160 Ala Pro Ala Pro Arg Pro Lys Phe Asp Pro Tyr Gly Gin Tyr Gly Arg 165 170 175 Tyr Gly Gin Tyr Gly Gin Tyr Gly Val Gin Pro Gly Gly Tyr Tyr Gly 180 185 190 Gin Gin Gly Ala Gin Gin Ala Ala Gly Leu Gin Ser Pro Gly Pro Gin 195 200 205 Gin Ser Pro Gin Pro Pro Gly Tyr Gly Ser Gin Tyr Gly Gly Tyr Ser 210 215 220 Ser Ser Pro Ser Gin Ser Gly Ser Gly Tyr Thr Ala Gin Pro Pro Ala 225 230 235 240 Gin Pro Pro Ala Gin Ser Gly Ser Gin Gin Ser His Gin Gly Pro Ser 245 250 255 Thr Pro Pro Thr Gly Phe Pro Ser Phe Ser Pro Pro Pro Pro Val Ser 260 265 270 Ala Gly Thr Gly Ser Gin Ala Gly Ser Ala Pro Val Asn Tyr Ser Asn 275 280 285 Pro Ser Gly Gly Glu Gin Ser Ser Ser Pro Gly Gly Ala Pro Val 290 295 300 (2) INFORMATION FOR SEQ ID N0:93: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 28 amino acids (B) TYPE: amino acid 129 (C) STRANDEDNESS: single (D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID N0:93: Gly Cys Gly Glu Thr Asp Ala Ala Thr Leu Ala Gin Glu Ala Gly Asn 1 5 10 15 Phe Glu Arg Ile Ser Gly Asp Leu Lys Thr Gin He 20 25 (2) INFORMATION FOR SEQ ID NO:94: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 16 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID N0:94: Asp Gin Val Glu Ser Thr Ala Gly Ser Leu Gin Gly Gin Trp Arg Gly 1 5 10 15 (2) INFORMATION FOR SEQ ID NO:95: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 27 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID NO:95: Gly Cys Gly Ser Thr Ala Gly Ser Leu Gin Gly Gin Trp Arg Gly Ala 1 5 10 15 Ala Gly Thr Ala Ala Gin Ala Ala Val Val Arg 20 25 (2) INFORMATION FOR SEQ ID NO:96: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 27 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID N0:96: Gly Cys Gly Gly Thr Ala Ala Gin Ala Ala Val Val Arg Phe Gin Glu 1 5 10 15 Ala Ala Asn Lys Gin Lys Gin Glu Leu Asp Glu 20 25 (2) INFORMATION FOR SEQ ID NO:97: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 27 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID N0:97: Gly Cys Gly Ala Asn Lys Gin Lys Gin Glu Leu Asp Glu He Ser Thr 1 5 10 15 131 Asn Ile Arg Gin Ala Gly Val Gin Tyr Ser Arg 20 25 (2) INFORMATION FOR SEQ ID NO:98: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 28 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID N0:98: Gly Cys Gly He Arg Gin Ala Gly Val Gin Tyr Ser Arg Ala Asp Glu 1 5 10 15 Glu Gin Gin Gin Ala Leu Ser Ser Gin Met Gly Phe 20 25 (2) INFORMATION FOR SEQ ID NO:99: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 507 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID N0:99: ATGAAGATGG TGAAATCGAT CGCCGCAGGT CTGACCGCCG CGGCTGCAAT CGGCGCCGCT 60 GCGGCCGGTG TGACπCGAT CATGGCTGGC GGCCCGGTCG TATACCAGAT GCAGCCGGTC 120 GTCπCGGCG CGCCACTGCC GπGGACCCG GCATCCGCCC CTGACGTCCC GACCGCCGCC 180 CAGπGACCA GCCTGCTCAA CAGCCTCGCC GATCCCAACG TGTCGπTGC GAACAAGGGC 240 AGTCTGGTCG AGGGCGGCAT CGGGGGCACC GAGGCGCGCA TCGCCGACCA CAAGCTGAAG 300 AAGGCCGCCG AGCACGGGGA TCTGCCGCTG TCGπCAGCG TGACGAACAT CCAGCCGGCG 360 GCCGCCGGπ CGGCCACCGC CGACGπTCC GTCTCGGGTC CGAAGCTCTC GTCGCCGGTC 420 ACGCAGAACG TCACGπCGT GAATCAAGGC GGCTGGATGC TGTCACGCGC ATCGGCGATG 480 GAGπGCTGC AGGCCGCAGG GAACTGA 507 (2) INFORMATION FOR SEQ ID NO:100: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 168 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID NO:100: Met Lys Met Val Lys Ser Ile Ala Ala Gly Leu Thr Ala Ala Ala Ala 1 5 10 15 Ile Gly Ala Ala Ala Ala Gly Val Thr Ser Ile Met Ala Gly Gly Pro 20 25 30 Val Val Tyr Gin Met Gin Pro Val Val Phe Gly Ala Pro Leu Pro Leu 35 40 45 Asp Pro Ala Ser Ala Pro Asp Val Pro Thr Ala Ala Gin Leu Thr Ser 50 55 60 Leu Leu Asn Ser Leu Ala Asp Pro Asn Val Ser Phe Ala Asn Lys Gly 65 70 75 80 Ser Leu Val Glu Gly Gly He Gly Gly Thr Glu Ala Arg He Ala Asp 85 90 95 His Lys Leu Lys Lys Ala Ala Glu His Gly Asp Leu Pro Leu Ser Phe 100 105 110 133 Ser Val Thr Asn He Gin Pro Ala Ala Ala Gly Ser Ala Thr Ala Asp 115 120 125 Val Ser Val Ser Gly Pro Lys Leu Ser Ser Pro Val Thr Gin Asn Val 130 135 140 Thr Phe Val Asn Gin Gly Gly Trp Met Leu Ser Arg Ala Ser Ala Met 145 150 155 160 Glu Leu Leu Gin Ala Ala Gly Asn 165 (2) INFORMATION FOR SEQ ID NO:101: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 500 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID NO:101: CGTGGCAATG TCGπGACCG TCGGGGCCGG GGTCGCCTCC GCAGATCCCG TGGACGCGGT 60 CAπAACACC ACCTGCAAπ ACGGGCAGGT AGTAGCTGCG CTCAACGCGA CGGATCCGGG 120 GGCTGCCGCA CAGπCAACG CCTCACCGGT GGCGCAGTCC TATπGCGCA ATTTCCTCGC 180 CGCACCGCCA CCTCAGCGCG CTGCCATGGC CGCGCAAπG CAAGCTGTGC CGGGGGCGGC 240 ACAGTACATC GGCCπGTCG AGTCGGπGC CGGCTCCTGC AACAACTAπ AAGCCCATGC 300 GGGCCCCATC CCGCGACCCG GCATCGTCGC CGGGGCTAGG CCAGAπGCC CCGCTCCTCA 360 ACGGGCCGCA TCCCGCGACC CGGCATCGTC GCCGGGGCTA GGCCAGAπG CCCCGCTCCT 420 CAACGGGCCG CATCTCGTGC CGAAπCCTG CAGCCCGGGG GATCCACTAG πCTAGAGCG 480 GCCGCCACCG CGGTGGAGCT 500 134 (2) INFORMATION FOR SEQ ID NO:102: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 96 amino acids (B~) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID NO:102: Val Ala Met Ser Leu Thr Val Gly Ala Gly Val Ala Ser Ala Asp Pro 1 5 10 15 Val Asp Ala Val He Asn Thr Thr Cys Asn Tyr Gly Gin Val Val Ala 20 25 30 Ala Leu Asn Ala Thr Asp Pro Gly Ala Ala Ala Gin Phe Asn Ala Ser 35 40 45 Pro Val Ala Gin Ser Tyr Leu Arg Asn Phe Leu Ala Ala Pro Pro Pro 50 55 60 Gin Arg Ala Ala Met Ala Ala Gin Leu Gin Ala Val Pro Gly Ala Ala 65 70 75 80 Gin Tyr Ile Gly Leu Val Glu Ser Val Ala Gly Ser Cys Asn Asn Tyr 85 90 95 (2) INFORMATION FOR SEQ ID NO:103: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 154 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID NO:103: 135 ATGACAGAGC AGCAGTGGAA TTTCGCGGGT ATCGAGGCCG CGGCAAGCGC AATCCAGGGA 60 AATGTCACGT CCAπCAπC CCTCCπGAC GAGGGGAAGC AGTCCCTGAC CAAGCTCGCA 120 GCGGCCTGGG GCGGTAGCGG πCGGAAGCG TACC 154 (2) INFORMATION FOR SEQ ID NO:104: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 51 amino acids (B) TYPE: amino acid (0 STRANDEDNESS : single (D) TOPOLOGY: l i near (xi ) SEQUENCE DESCRIPTION: SEQ ID NO: 104: Met Thr Glu Gin Gin Trp Asn Phe Ala Gly Ile Glu Ala Ala Ala Ser 1 5 10 15 Ala He Gin Gly Asn Val Thr Ser Ile His Ser Leu Leu Asp Glu Gly 20 25 30 Lys Gin Ser Leu Thr Lys Leu Ala Al a Ala Trp Gly Gly Ser Gly Ser 35 40 45 Glu Ala Tyr 50 (2) INFORMATION FOR SEQ ID NO:105: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 282 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear 136 (xi ) SEQUENCE DESCRIPTION : SEQ ID NO: 105: CGGTCGCGCA CπCCAGGTG ACTATGAAAG TCGGCTTCCG NCTGGAGGAT TCCTGAACCT 60 TCAAGCGCGG CCGATAACTG AGGTGCATCA πAAGCGACT πTCCAGAAC ATCCTGACGC 120 GCTCGAAACG CGGCACAGCC GACGGTGGCT CCGNCGAGGC GCTGNCTCCA AAATCCCTGA 180 GACAAπCGN CGGGGGCGCC TACAAGGAAG TCGGTGCTGA AπCGNCGNG TATCTGGTCG 240 ACCTGTGTGG TCTGNAGCCG GACGAAGCGG TGCTCGACGT CG 282 (2) INFORMATION FOR SEQ ID NO: 106: (i ) SEQUENCE CHARACTERISTICS : (A) LENGTH : 1565 base pai rs (B) TYPE : nucl ei c aci d (C) STRANDEDNESS : si ngle (D) TOPOLOGY: l i near (xi ) SEQUENCE DESCRIPTION: SEQ ID N0: 106: GTATGCGGCC ACTGAAGTCG CCAATGCGGC GGCGGCCAGC TAAGCCAGGA ACAGTCGGCA 60 CGAGAAACCA CGAGAAATAG GGACACGTAA TGGTGGATTT CGGGGCGπA CCACCGGAGA 120 TCAACTCCGC GAGGATGTAC GCCGGCCCGG GπCGGCCTC GCTGGTGGCC GCGGCTCAGA 180 TGTGGGACAG CGTGGCGAGT GACCTGTπT CGGCCGCGTC GGCGTπCAG TCGGTGGTCT 240 GGGGTCTGAC GGTGGGGTCG TGGATAGGπ CGTCGGCGGG TCTGATGGTG GCGGCGGCCT 300 CGCCGTATGT GGCGTGGATG AGCGTCACCG CGGGGCAGGC CGAGCTGACC GCCGCCCAGG 360 TCCGGGπGC TGCGGCGGCC TACGAGACGG CGTATGGGCT GACGGTGCCC CCGCCGGTGA 420 TCGCCGAGAA CCGTGCTGAA CTGATGAπC TGATAGCGAC CAACCTCπG GGGCAAAACA 480 CCCCGGCGAT CGCGGTCAAC GAGGCCGAAT ACGGCGAGAT GTGGGCCCAA GACGCCGCCG 540 CGATGTπGG CTACGCCGCG GCGACGGCGA CGGCGACGGC GACGπGCTG CCGπCGAGG 600 AGGCGCCGGA GATGACCAGC GCGGGTGGGC TCCTCGAGCA GGCCGCCGCG GTCGAGGAGG 660 CCTCCGACAC CGCCGCGGCG AACCAGπGA TGAACAATGT GCCCCAGGCG CTGCAACAGC 720 TGGCCCAGCC CACGCAGGGC ACCACGCCπ CπCCAAGCT GGGTGGCCTG TGGAAGACGG 780 TCTCGCCGCA TCGGTCGCCG ATCAGCAACA TGGTGTCAAT GGCCAACAAC CACATGTCAA 840 TGACCAACTC GGGTGTGTCA ATGACCAACA CCπGAGCTC GATGπGAAG GGCπTGCTC 900 CGGCGGCGGC CGCCCAGGCC GTGCAAACCG CGGCGCAAAA CGGGGTCCGG GCGATGAGCT 960 CGCTGGGCAG CTCGCTGGGT TCπCGGGTC TGGGCGGTGG GGTGGCCGCC AACπGGGTC 1020 GGGCGGCCTC GGTCGGπCG πGTCGGTGC CGCAGGCCTG GGCCGCGGCC AACCAGGCAG 1080 TCACCCCGGC GGCGCGGGCG CTGCCGCTGA CCAGCCTGAC CAGCGCCGCG GAAAGAGGGC 1140 CCGGGCAGAT GCTGGGCGGG CTGCCGGTGG GGCAGATGGG CGCCAGGGCC GGTGGTGGGC 1200 TCAGTGGTGT GCTGCGTGπ CCGCCGCGAC CCTATGTGAT GCCGCAπCT CCGGCGGCCG 1260 GCTAGGAGAG GGGGCGCAGA CTGTCGπAT πGACCAGTG ATCGGCGGTC TCGGTGTTTC 1320 CGCGGCCGGC TATGACAACA GTCAATGTGC ATGACAAGπ ACAGGTAπA GGTCCAGGπ 1380 CAACAAGGAG ACAGGCAACA TGGCCTCACG TπTATGACG GATCCGCACG CGATGCGGGA 1440 CATGGCGGGC CGTπTGAAG TGCACGCCCA GACGGTGGAG GACGAGGCTC GCCGGATGTG 1500 GGCGTCCGCG CAAAACATTT CCGGTGCGGG CTGGAGTGGC ATGGCCGAGG CGACCTCGCT 1560 AGACA 1565 (2) INFORMATION FOR SEQ ID NO: 107 : (i ) SEQUENCE CHARACTERISTICS : (A) LENGTH : 391 ami no acids (B) TYPE : amino acid (C) STRANDEDNESS : single (D) TOPOLOGY: l i near O 97/09428 138 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:107: Met VaT Asp Phe Gly Ala Leu Pro Pro Glu He Asn Ser Ala Arg Met 1 5 10 15 Tyr Ala Gly Pro Gly Ser Ala Ser Leu Val Ala Ala Ala Gin Met Trp 20 25 30 Asp Ser Val Ala Ser Asp Leu Phe Ser Ala Ala Ser Ala Phe Gin Ser 35 40 45 Val Val Trp Gly Leu Thr Val Gly Ser Trp He Gly Ser Ser Ala Gly 50 55 60 Leu Met Val Ala Ala Ala Ser Pro Tyr Val Ala Trp Met Ser Val Thr 65 70 75 80 Ala Gly Gin Ala Glu Leu Thr Ala Ala Gin Val Arg Val Ala Ala Ala 85 90 95 Ala Tyr Glu Thr Ala Tyr Gly Leu Thr Val Pro Pro Pro Val Ile Ala 100 105 110 Glu Asn Arg Ala Glu Leu Met Ile Leu Ile Ala Thr Asn Leu Leu Gly 115 120 125 Gin Asn Thr Pro Ala Ile Ala Val Asn Glu Ala Glu Tyr Gly Glu Met 130 135 140 Trp Ala Gin Asp Ala Ala Ala Met Phe Gly Tyr Ala Ala Ala Thr Ala 145 150 155 160 Thr Ala Thr Ala Thr Leu Leu Pro Phe Glu Glu Ala Pro Glu Met Thr 165 170 175 Ser Ala Gly Gly Leu Leu Glu Gin Ala Ala Ala Val Glu Glu Ala Ser 180 185 190 Asp Thr Ala Ala Ala Asn Gin Leu Met Asn Asn Val Pro Gin Ala Leu 195 200 205 Gin Gin Leu Ala Gin Pro Thr Gin Gly Thr Thr Pro Ser Ser Lys Leu 210 215 220 Gly Gly Leu Trp Lys Thr Val Ser Pro His Arg Ser Pro He Ser Asn 225 230 235 240 Met Val Ser Met Ala Asn Asn His Met Ser Met Thr Asn Ser Gly Val 245 250 255 Ser Met Thr Asn Thr Leu Ser Ser Met Leu Lys Gly Phe Ala Pro Ala 260 265 270 Ala Ala Ala Gin Ala Val Gin Thr Ala Ala Gin Asn Gly Val Arg Ala 275 280 285 Met Ser Ser Leu Gly Ser Ser Leu Gly Ser Ser Gly Leu Gly Gly Gly 290 295 300 Val Ala Ala Asn Leu Gly Arg Ala Ala Ser Val Gly Ser Leu Ser Val 305 310 315 320 Pro Gin Ala Trp Ala Ala Ala Asn Gin Ala Val Thr Pro Ala Ala Arg 325 330 335 Ala Leu Pro Leu Thr Ser Leu Thr Ser Ala Ala Glu Arg Gly Pro Gly 340 345 350 Gin Met Leu Gly Gly Leu Pro Val Gly Gin Met Gly Ala Arg Ala Gly 355 360 365 Gly Gly Leu Ser Gly Val Leu Arg Val Pro Pro Arg Pro Tyr Val Met 370 375 380 Pro His Ser Pro Ala Ala Gly 385 390 (2) INFORMATION FOR SEQ ID NO:108: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 259 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear 140 (xi) SEQUENCE DESCRIPTION: SEQ ID NO:108: ACCAACACCT TGCACTCNAT GπGAAGGGC πAGCTCCGG CGGCGGCTCA GGCCGTGGAA 60 ACCGCGGCGG AAAACGGGGT CTGGGCAATG AGCTCGCTGG GCAGCCAGCT GGGπCGTCG 120 CTGGGπcπ CGGGTCTGGG CGCTGGGGTG GCCGCCAACT TGGGTCGGGC GGCCTCGGTC 180 GGπCGπGT CGGTGCCGCC AGCATGGGCC GCGGCCAACC AGGCGGTCAC CCCGGCGGCG 240 CGGGCGCTGC CGCTGACCA 259 (2) INFORMATION FOR SEQ ID NO:109: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 86 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID NO:109: Thr Asn Thr Leu His Ser Met Leu Lys Gly Leu Ala Pro Ala Ala Ala 1 5 10 15 Gin Ala Val Glu Thr Ala Ala Glu Asn Gly Val Trp Ala Met Ser Ser 20 25 30 Leu Gly Ser Gin Leu Gly Ser Ser Leu Gly Ser Ser Gly Leu Gly Ala 35 40 45 Gly Val Ala Ala Asn Leu Gly Arg Ala Ala Ser Val Gly Ser Leu Ser 50 55 60 Val Pro Pro Ala Trp Ala Ala Ala Asn Gin Ala Val Thr Pro Ala Ala 65 70 75 80 Arg Ala Leu Pro Leu Thr 85 (2) INFORMATION FOR SEQ ID NO: 110 : ( i ) SEQUENCE CHARACTERISTICS : (A) LENGTH : 1109 base pai rs ( B) TYPE : nucl ei c aci d (C) STRANDEDNESS : si ngl e ( D) TOPOLOGY : l i near (xi ) SEQUENCE DESCRIPTION : SEQ ID NO : 110 : TACπGAGAG AATTTGACCT GπGCCGACG πGπTGCTG TCCATCAπG GTGCTAGπA 60 TGGCCGAGCG GAAGGAπAT CGAAGTGGTG GACπCGGGG CGπACCACC GGAGATCAAC 120 TCCGCGAGGA TGTACGCCGG CCCGGGπCG GCCTCGCTGG TGGCCGCCGC GAAGATGTGG 180 GACAGCGTGG CGAGTGACCT GTπTCGGCC GCGTCGGCGT πCAGTCGGT GGTCTGGGGT 240 CTGACGACGG GATCGTGGAT AGGπCGTCG GCGGGTCTGA TGGTGGCGGC GGCCTCGCCG 300 TATGTGGCGT GGATGAGCGT CACCGCGGGG CAGGCCGAGC TGACCGCCGC CCAGGTCCGG 360 GπGCTGCGG CGGCCTACGA GACGGCGTAT GGGCTGACGG TGCCCCCGCC GGTGATCGCC 420 GAGAACCGTG CTGAACTGAT GAπCTGATA GCGACCAACC TCπGGGGCA AAACACCCCG 480 GCGATCGCGG TCAACGAGGC CGAATACGGG GAGATGTGGG CCCAAGACGC CGCCGCGATG 540 TTTGGCTACG CCGCCACGGC GGCGACGGCG ACCGAGGCGT TGCTGCCGπ CGAGGACGCC 600 CCACTGATCA CCAACCCCGG CGGGCTCCπ GAGCAGGCCG TCGCGGTCGA GGAGGCCATC 660 GACACCGCCG CGGCGAACCA GπGATGAAC AATGTGCCCC AAGCGCTGCA ACAACTGGCC 720 CAGCCCACGA AAAGCATCTG GCCGπCGAC CAACTGAGTG AACTCTGGAA AGCCATCTCG 780 CCGCATCTGT CGCCGCTCAG CAACATCGTG TCGATGCTCA ACAACCACGT GTCGATGACC 840 AACTCGGGTG TGTCAATGGC CAGCACCπG CACTCAATGT TGAAGGGCπ TGCTCCGGCG 900 GCGGCTCAGG CCGTGGAAAC CGCGGCGCAA AACGGGGTCC AGGCGATGAG CTCGCTGGGC 960 AGCCAGCTGG GπCGTCGCT GGGπcπCG GGTCTGGGCG CTGGGGTGGC CGCCAACπG 1020 GGTCGGGCGG CCTCGGTCGG πCGπGTCG GTGCCGCAGG CCTGGGCCGC GGCCAACCAG 1080 GCGGTCACCC CGGCGGCGCG GGCGCTGCC 1109 (2) INFORMATION FOR SEQ ID NO:111: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 341 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID NO:111: Val Val Asp Phe Gly Ala Leu Pro Pro Glu Ile Asn Ser Ala Arg Met 1 5 10 15 Tyr Ala Gly Pro Gly Ser Ala Ser Leu Val Ala Ala Ala Lys Met Trp 20 25 30 Asp Ser Val Ala Ser Asp Leu Phe Ser Ala Ala Ser Ala Phe Gin Ser 35 40 45 Val Val Trp Gly Leu Thr Thr Gly Ser Trp Ile Gly Ser Ser Ala Gly 50 55 60 Leu Met Val Ala Ala Ala Ser Pro Tyr Val Ala Trp Met Ser Val Thr 65 70 75 80 Ala Gly Gin Ala Glu Leu Thr Ala Ala Gin Val Arg Val Ala Ala Ala 85 90 95 Ala Tyr Glu Thr Ala Tyr Gly Leu Thr Val Pro Pro Pro Val Ile Ala 100 105 110 Glu Asn Arg Ala Glu Leu Met Ile Leu Ile Ala Thr Asn Leu Leu Gly 115 120 125 Gin Asn Thr Pro Ala He Ala Val Asn Glu Ala Glu Tyr Gly Glu Met 130 135 140 Trp Ala Gin Asp Ala Ala Ala Met Phe Gly Tyr Ala Ala Thr Ala Ala 145 150 155 160 Thr Ala Thr Glu Ala Leu Leu Pro Phe Glu Asp Ala Pro Leu He Thr 165 170 175 Asn Pro Gly Gly Leu Leu Glu Gin Ala Val Ala Val Glu Glu Ala He 180 185 190 Asp Thr Ala Ala Ala Asn Gin Leu Met Asn Asn Val Pro Gin Ala Leu 195 200 205 Gin Gin Leu Ala Gin Pro Thr Lys Ser Ile Trp Pro Phe Asp Gin Leu 210 215 220 Ser Glu Leu Trp Lys Ala Ile Ser Pro His Leu Ser Pro Leu Ser Asn 225 230 235 240 Ile Val Ser Met Leu Asn Asn His Val Ser Met Thr Asn Ser Gly Val 245 250 255 Ser Met Ala Ser Thr Leu His Ser Met Leu Lys Gly Phe Ala Pro Ala 260 265 270 Ala Ala Gin Ala Val Glu Thr Ala Ala Gin Asn Gly Val Gin Ala Met 275 280 285 Ser Ser Leu Gly Ser Gin Leu Gly Ser Ser Leu Gly Ser Ser Gly Leu 290 295 300 Gly Ala Gly Val Ala Ala Asn Leu Gly Arg Ala Ala Ser Val Gly Ser 305 310 315 320 Leu Ser Val Pro Gin Ala Trp Ala Ala Ala Asn Gin Ala Val Thr Pro 325 330 335 Ala Ala Arg Ala Leu 340 (2) INFORMATION FOR SEQ ID NO:112: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH : 1256 base pai rs (B) TYPE : nucl ei c aci d (C) STRANDEDNESS : si ngl e (D) TOPOLOGY: l i near (xi ) SEQUENCE DESCRIPTION : SEQ ID NO: 112 : CATCGGAGGG AGTGATCACC ATGCTGTGGC ACGCAATGCC ACCGGAGNTA AATACCGCAC 60 GGCTGATGGC CGGCGCGGGT CCGGCTCCAA TGCTTGCGGC GGCCGCGGGA TGGCAGACGC 120 TTTCGGCGGC TCTGGACGCT CAGGCCGTCG AGπGACCGC GCGCCTGAAC TCTCTGGGAG 180 AAGCCTGGAC TGGAGGTGGC AGCGACAAGG CGCπGCGGC TGCAACGCCG ATGGTGGTCT 240 GGCTACAAAC CGCGTCAACA CAGGCCAAGA CCCGTGCGAT GCAGGCGACG GCGCAAGCCG 300 CGGCATACAC CCAGGCCATG GCCACGACGC CGTCGCTGCC GGAGATCGCC GCCAACCACA 360 TCACCCAGGC CGTCCπACG GCCACCAACT TCπCGGTAT CAACACGATC CCGATCGCGT 420 TGACCGAGAT GGAπAπTC ATCCGTATGT GGAACCAGGC AGCCCTGGCA ATGGAGGTCT 480 ACCAGGCCGA GACCGCGGπ AACACGCπT TCGAGAAGCT CGAGCCGATG GCGTCGATCC 540 πGATCCCGG CGCGAGCCAG AGCACGACGA ACCCGATCπ CGGAATGCCC TCCCCTGGCA 600 GCTCAACACC GGπGGCCAG πGCCGCCGG CGGCTACCCA GACCCTCGGC CAACTGGGTG 660 AGATGAGCGG CCCGATGCAG CAGCTGACCC AGCCGCTGCA GCAGGTGACG TCGπGπCA ' 720 GCCAGGTGGG CGGCACCGGC GGCGGCAACC CAGCCGACGA GGAAGCCGCG CAGATGGGCC 780 TGCTCGGCAC CAGTCCGCTG TCGAACCATC CGCTGGCTGG TGGATCAGGC CCCAGCGCGG 840 GCGCGGGCCT GCTGCGCGCG GAGTCGCTAC CTGGCGCAGG TGGGTCGπG ACCCGCACGC 900 CGCTGATGTC TCAGCTGATC GAAAAGCCGG πGCCCCCTC GGTGATGCCG GCGGCTGCTG 960 CCGGATCGTC GGCGACGGGT GGCGCCGCTC CGGTGGGTGC GGGAGCGATG GGCCAGGGTG 1020 CGCAATCCGG CGGCTCCACC AGGCCGGGTC TGGTCGCGCC GGCACCGCTC GCGCAGGAGC 1080 GTGAAGAAGA CGACGAGGAC GACTGGGACG AAGAGGACGA CTGGTGAGCT CCCGTAATGA 1140 CAACAGACπ CCCGGCCACC CGGGCCGGAA GAOTGCCAA CATπTGGCG AGGAAGGTAA 1200 AGAGAGAAAG TAGTCCAGCA TGGCAGAGAT GAAGACCGAT GCCGCTACCC TCGCGC 1256 (2) INFORMATION FOR SEQ ID NO: 113: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 432 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID NO:113: CTAGTGGATG GGACCATGGC CATπTCTGC AGTCTCACTG CCπCTGTGT TGACATTπG 60 GCACGCCGGC GGAAACGAAG CACTGGGGTC GAAGAACGGC TGCGCTGCCA TATCGTCCGG 120 AGCπCCATA CCπCGTGCG GCCGGAAGAG CπGTCGTAG TCGGCCGCCA TGACAACCTC 180 TCAGAGTGCG CTCAAACGTA TAAACACGAG AAAGGGCGAG ACCGACGGAA GGTCGAACTC 240 GCCCGATCCC GTGTπCGCT AπCTACGCG AACTCGGCGT TGCCCTATGC GAACATCCCA 300 GTGACGπGC CπCGGTCGA AGCCAπGCC TGACCGGCπ CGCTGATCGT CCGCGCCAGG 360 πCTGCAGCG CGπGπCAG CTCGGTAGCC GTGGCGTCCC ATππGCTG GACACCCTGG 420 TACGCCTCCG AA 432 (2) INFORMATION FOR SEQ ID NO: 114: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 368 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID NO:114: Met Leu Trp His Ala Met Pro Pro Glu Xaa Asn Thr Ala Arg Leu Met 1 5 10 15 Ala Gly Ala Gly Pro Ala Pro Met Leu Ala Ala Ala Ala Gly Trp Gin 20 25 30 Thr Leu Ser Ala Ala Leu Asp Ala Gin Ala Val Glu Leu Thr Ala Arg 35 40 45 Leu Asn Ser Leu Gly Glu Ala Trp Thr Gly Gly Gly Ser Asp Lys Ala 50 55 60 Leu Ala Ala Ala Thr Pro Met Val Val Trp Leu Gin Thr Ala Ser Thr 65 70 75 80 Gin Ala Lys Thr Arg Ala Met Gin Ala Thr Ala Gin Ala Ala Ala Tyr 85 90 95 Thr Gin Ala Met Ala Thr Thr Pro Ser Leu Pro Glu Ile Ala Ala Asn 100 105 110 His Ile Thr Gin Ala Val Leu Thr Ala Thr Asn Phe Phe Gly Ile Asn 115 120 125 Thr Ile Pro Ile Ala Leu Thr Glu Met Asp Tyr Phe Ile Arg Met Trp 130 135 140 Asn Gin Ala Ala Leu Ala Met Glu Val Tyr Gin Ala Glu Thr Ala Val 145 150 155 160 Asn Thr Leu Phe Glu Lys Leu Glu Pro Met Ala Ser Ile Leu Asp Pro 165 170 175 Gly Ala Ser Gin Ser Thr Thr Asn Pro He Phe Gly Met Pro Ser Pro 180 185 190 Gly Ser Ser Thr Pro Val Gly Gin Leu Pro Pro Ala Ala Thr Gin Thr 195 200 205 Leu Gly Gin Leu Gly Glu Met Ser Gly Pro Met Gin Gin Leu Thr Gin 210 215 220 Pro Leu Gin Gin Val Thr Ser Leu Phe Ser Gin Val Gly Gly Thr Gly 225 230 235 240 Gly Gly Asn Pro Ala Asp Glu Glu Ala Ala Gin Met Gly Leu Leu Gly 245 250 255 Thr Ser Pro Leu Ser Asn His Pro Leu Ala Gly Gly Ser Gly Pro Ser 260 265 270 Ala Gly Ala Gly Leu Leu Arg Ala Glu Ser Leu Pro Gly Ala Gly Gly 275 280 285 Ser Leu Thr Arg Thr Pro Leu Met Ser Gin Leu Ile Glu Lys Pro Val 290 295 300 Ala Pro Ser Val Met Pro Ala Ala Ala Ala Gly Ser Ser Ala Thr Gly 305 310 315 320 Gly Ala Ala Pro Val Gly Ala Gly Ala Met Gly Gin Gly Ala Gin Ser 325 330 335 Gly Gly Ser Thr Arg Pro Gly Leu Val Ala Pro Ala Pro Leu Ala Gin 340 345 350 Glu Arg Glu Glu Asp Asp Glu Asp Asp Trp Asp Glu Glu Asp Asp Trp 355 360 365 (2) INFORMATION FOR SEQ ID NO:115: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 12 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID NO:115: Met Ala Glu Met Lys Thr Asp Ala Ala Thr Leu Ala 1 5 10 (2) INFORMAnON FOR SEQ ID NO:116: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 396 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID NO:116: GATCTCCGGC GACCTGAAAA CCCAGATCGA CCAGGTGGAG TCGACGGCAG GπCGπGCA 60 GGGCCAGTGG CGCGGCGCGG CGGGGACGGC CGCCCAGGCC GCGGTGGTGC GCπCCAAGA 120 AGCAGCCAAT AAGCAGAAGC AGGAACTCGA CGAGATCTCG ACGAATAπC GTCAGGCCGG 180 CGTCCAATAC TCGAGGGCCG ACGAGGAGCA GCAGCAGGCG CTGTCCTCGC AAATGGGCπ 240 CTGACCCGCT AATACGAAAA GAAACGGAGC AAAAACATGA CAGAGCAGCA GTGGAATTTC 300 GCGGGTATCG AGGCCGCGGC AAGCGCAATC CAGGGAAATG TCACGTCCAT TCAπCCCTC 360 CπGACGAGG GGAAGCAGTC CCTGACCAAG CTCGCA 396 (2) INFORMATION FOR SEQ ID NO:117: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 80 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID NO:117: He Ser Gly Asp Leu Lys Thr Gin Ile Asp Gin Val Glu Ser Thr Ala 1 5 10 15 Gly Ser ' Leu Gin Gly Gin Trp Arg Gly Ala Ala Gly Thr Ala Ala Gin 20 25 30 Ala Ala Val Val Arg Phe Gin Glu Ala Ala Asn Lys Gin Lys Gin Glu 35 40 45 Leu Asp Glu Ile Ser Thr Asn He Arg Gin Ala Gly Val Gin Tyr Ser 50 55 60 Arg Ala Asp Glu Glu Gin Gin Gin Ala Leu Ser Ser Gin Met Gly Phe 65 70 75 80 (2) INFORMATION FOR SEQ ID NO:118: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 387 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID NO:118: GTGGATCCCG ATCCCGTGπ TCGCTAπCT ACGCGAACTC GGCGπGCCC TATGCGAACA 60 TCCCAGTGAC GπGCCπCG GTCGAAGCCA πGCCTGACC GGCπCGCTG ATCGTCCGCG 120 CCAGGπCTG CAGCGCGπG πCAGCTCGG TAGCCGTGGC GTCCCATTπ TGCTGGACAC 180 CCTGGTACGC CTCCGAACCG CTACCGCCCC AGGCCGCTGC GAGCπGGTC AGGGACTGCT 240 TCCCCTCGTC AAGGAGGGAA TGAATGGACG TGACATπCC CTGGAπGCG CπGCCGCGG 300 CCTCGATACC CGCGAAAπC CACTGCTGCT CTGTCATGπ lTTGCTCCGT πcπTTCGT 360 AπAGCGGGT CAGAAGCCCA TTTGCGA 387 (2) INFORMATION FOR SEQ ID NO:119: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 272 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID NO:119: CGGCACGAGG ATCTCGGπG GCCCAACGGC GCTGGCGAGG GCTCCGπCC GGGGGCGAGC 60 TGCGCGCCGG ATGCπCCTC TGCCCGCAGC CGCGCCTGGA TGGATGGACC AGπGCTACC 120 πCCCGACGT πCGπCGGT GTCTGTGCGA TAGCGGTGAC CCCGGCGCGC ACGTCGGGAG 180 TGπGGGGGG CAGGCCGGGT CGGTGGπCG GCCGGGGACG CAGACGGTCT GGACGGAACG 240 GGCGGGGGπ CGCCGAπGG CATCTTTGCC CA 272 (2) INFORMATION FOR SEQ ID NO:120: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 20 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID NO:120: Asp Pro Val Asp Ala Val Ile Asn Thr Thr Cys Asn Tyr Gly Gin Val 1 5 10 15 Val Ala Ala Leu 20 (2) INFORMATION FOR SEQ ID NO:121: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 15 amino acids (B) TYPE: amino acid (0 STRANDEDNESS: (D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID NO:121: Ala Val Glu Ser Gly Met Leu Ala Leu Gly Thr Pro Ala Pro Ser 1 5 10 15 (2) INFORMATION FOR SEQ ID NO:122: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 19 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID NO:122: Ala Ala Met Lys Pro Arg Thr Gly Asp Gly Pro Leu Glu Ala Ala Lys 1 5 10 15 Glu Gly Arg (2) INFORMATION FOR SEQ ID NO:123: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 15 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID N0:123: Tyr Tyr Trp Cys Pro Gly Gin Pro Phe Asp Pro Ala Trp Gly Pro 1 5 10 15 (2) INFORMATION FOR SEQ ID NO:124: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 14 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID N0:124: Asp Ile Gly Ser Glu Ser Thr Glu Asp Gin Gin Xaa Ala Val 1 5 10 (2) INFORMATION FOR SEQ ID NO:125: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 13 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID NO:125: Ala Glu Glu Ser He Ser Thr Xaa Glu Xaa Ile Val Pro 1 5 10 (2) INFORMATION FOR SEQ ID NO:126: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 17 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID NO:126: Asp Pro Glu Pro Ala Pro Pro Val Pro Thr Thr Ala Ala Ser Pro Pro 1 5 10 15 Ser (2) INFORMATION FOR SEQ ID NO:127: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 15 amino acids (B) TYPE: amino acid (0 STRANDEDNESS: (D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID NO:127: Ala Pro Lys Thr Tyr Xaa Glu Glu Leu Lys Gly Thr Asp Thr Gly 1 5 10 15 (2) INFORMATION FOR SEQ ID NO:128: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 30 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID N0:128: Asp Pro Ala Ser Ala Pro Asp Val Pro Thr Ala Ala Gin Leu Thr Ser 1 "" 5 10 15 Leu Leu Asn Ser Leu Ala Asp Pro Asn Val Ser Phe Ala Asn 20 25 30 (2) INFORMATION FOR SEQ ID NO:129: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 22 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID NO:129: Asp Pro Pro Asp Pro His Gin Xaa Asp Met Thr Lys Gly Tyr Tyr Pro 1 5 10 15 Gly Gly Arg Arg Xaa Phe 20 (2) INFORMATION FOR SEQ ID NO:130: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 7 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID NO:130: Asp Pro Gly Tyr Thr Pro Gly 1 5 (2) INFORMATION FOR SEQ ID NO:131: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 10 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ix) FEATURE: (D) OTHER INFORMATION: /note- "The Second Residue Can Be Either a Pro or Thr" (xi) SEQUENCE DESCRIPTION: SEQ ID NO:131: Xaa Xaa Gly Phe Thr Gly Pro Gin Phe Tyr 1 5 10 (2) INFORMATION FOR SEQ ID NO:132: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 9 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (ix) FEATURE: (D) OTHER INFORMATION: /note- "The Third Residue Can Be Either a Gin or Leu" (xi) SEQUENCE DESCRIPTION: SEQ ID NO:132: Xaa Pro Xaa Val Thr Ala Tyr Ala Gly 1 ■ 5 (2) INFORMATION FOR SEQ ID NO:133: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 9 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID NO:133: Xaa Xaa Xaa Glu Lys Pro Phe Leu Arg 1 5 (2) INFORMATION FOR SEQ ID NO:134: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 15 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID N0:134: Xaa Asp Ser Glu Lys Ser Ala Thr He Lys Val Thr Asp Ala Ser 1 5 10 15 (2) INFORMATION FOR SEQ ID NO: 135: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 15 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID NO:135: Ala Gly Asp Thr Xaa Ile Tyr Ile Val Gly Asn Leu Thr Ala Asp 1 5 10 15 (2) INFORMATION FOR SEQ ID NO:136: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 15 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID NO:136: Ala Pro Glu Ser Gly Ala Gly Leu Gly Gly Thr Val Gin Ala Gly 1 5 10 15 (2) INFORMATION FOR SEQ ID NO:137: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 21 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: (D) TOPOLOGY: linear (xi ) SEQUENCE DESCRIPTION : SEQ ID NO: 137 : Xaa Tyr H e Al a Tyr Xaa Thr Thr Al a Gly Ile Val Pro Gly Lys Ile 1 5 10 15 Asn Val Hi s Leu Val 20

Claims: Claims 1. A polypeptide comprising an immunogenic portion of a soluble M. tuberculosis antigen, or a variant of said antigen that differs only in conservative substitutions and/or modifications, wherein said antigen has an N-terminal sequence selected from the group consisting of: (a) Asp-Pro-Val-Asp-Ala-Nal-Ile-Asn-Thr-Thr-Cys-Asn-Tyr-Gly-Gln- Val-Nal-Ala-Ala-Leu; (SEQ ID No. 120) (b) Ala-Val-Glu-Ser-Gly-Met-Leu-Ala-Leu-Gly-Thr-Pro-Ala-Pro-Ser; (SEQ ID No. 121) (c) Ala-Ala-Met-Lys-Pro-Arg-Thr-Gly-Asp-Gly-Pro-Leu-Glu-Ala-Ala- Lys-Glu-Gly-Arg; (SEQ ID No. 122) (d) Tyr-Tyr-Trp-Cys-Pro-Gly-Gln-Pro-Phe-Asp-Pro-Ala-Trp-Gly-Pro; (SEQ ID No. 123) (e) Asp-Ile-Gly-Ser-Glu-Ser-Thr-Glu-Asp-Gln-Gln-Xaa-Ala-Val; (SEQ ID No. 124) (f) Ala-Glu-Glu-Ser-Ile-Ser-Thr-Xaa-Glu-Xaa-Ile-Val-Pro; (SEQ ID No. 125) (g) Asp-Pro-Glu-Pro-Ala-Pro-Pro-Val-Pro-Thr-Thr-Ala-Ala-Ser-Pro-Pro- Ser; (SEQ ID No. 126) (h) Ala-Pro-Lys-Thr-Tyr-Xaa-Glu-Glu-Leu-Lys-Gly-Thr-Asp-Thr-Gly; (SEQ ID No. 127) (i) Asp-Pro-Ala-Ser-Ala-Pro-Asp-Val-Pro-Thr-Ala-Ala-Gln-Leu-Thr-Ser- Leu-Leu-Asn-Ser-Leu-Ala-Asp-Pro-Asn-Val-Ser-Phe-Ala-Asn; (SEQ ID No. 128) and G) Ala-Pro-Glu-Ser-Gly-Ala-Gly-Leu-Gly-Gly-Thr-Val-Gln-Ala-Gly; (SEQ ID No. 136) wherein Xaa may be any amino acid. 2. A polypeptide comprising an immunogenic portion of an M. tuberculosis antigen, or a variant of said antigen that differs only in conservative substitutions and/or modifications, wherein said antigen has an N-terminal sequence selected from the group consisting of: (a) Asp-Pro-Pro-Asp-Pro-His-Gln-Xaa-Asp-Met-Thr-Lys-Gly-Tyr-Tyr- Pro-Gly-Gly-Arg-Arg-Xaa-Phe; (SEQ ID No. 129) and (b) Xaa-Tyr-Ile-Ala-Tyr-Xaa-Thr-Thr-Ala-Gly-Ile-Nal-Pro-Gly-Lys-Ile- Asn-Val-His-Leu-Nal; (SEQ ID No. 137), wherein Xaa may be any amino acid. 3. A polypeptide comprising an immunogenic portion of a soluble M. tuberculosis antigen, or a variant of said antigen that differs only in conservative substitutions and/or modifications, wherein said antigen comprises an amino acid sequence encoded by a DNA sequence selected from the group consisting of the sequences recited in SEQ ID Nos.: 1, 2, 4-10, 13-25, 52, 99 and 101, the complements of said sequences, and DNA sequences that hybridize to a sequence recited in SEQ ID Nos.: 1, 2, 4-10, 13-25, 52, 99 and 101 or a complement thereof under moderately stringent conditions. 4. A polypeptide comprising an immunogenic portion of a M. tuberculosis antigen, or a variant of said antigen that differs only in conservative substitutions and/or modifications, wherein said antigen comprises an amino acid sequence encoded by a DNA sequence selected from the group consisting of the sequences recited in SEQ ID Nos.: 26-51, the complements of said sequences, and DNA sequences that hybridize to a sequence recited in SEQ ID Nos.: 26-51 or a complement thereof under moderately stringent conditions. 5. A DNA molecule comprising a nucleotide sequence encoding a polypeptide according to any one of claims 1-4. 6. An expression vector comprising a DNA molecule according to claim 5. \ 7. A host cell transformed with an expression vector according to claim 6. 8. The host cell of claim 7 wherein the host cell is selected from the group consisting of E. coli, yeast and mammalian cells. 9. A pharmaceutical composition comprising one or more polypeptides according to any one of claims 1-4 and a physiologically acceptable carrier. 10. A pharmaceutical composition comprising one or more DNA molecules according to claim 5 and a physiologically acceptable carrier. 11. A pharmaceutical composition comprising one or more DNA sequences recited in SΕQ ID Nos.: 3, 11 and 12; and a physiologically acceptable carrier. 12. A vaccine comprising one or more polypeptides according to any one of claims 1-4 and a non-specific immune response enhancer. 13. A vaccine comprising: a polypeptide having an N-terminal sequence selected from the group consisting of sequences recited in SΕQ ID NO: 134 and 135; and a non-specific immune response enhancer. 14. A vaccine comprising : one or more polypeptides encoded by a DNA sequence selected from the group consisting of SΕQ ID Nos.: 3, 11 and 12, the complements of said sequences, and DNA sequences that hybridize to a sequence recited in SΕQ ID Nos.: 3, 11 and 12; and a non-specific immune response enhancer. 15. The vaccine of claims 12-14 wherein the non-specific immune response enhancer is an adjuvant. 16. A vaccine comprising one or more DNA molecules according to claim 5 and a non-specific immune response enhancer. 17. A vaccine comprising one or more DNA sequences recited in SEQ ID Nos.: 3, 11 and 12; and a non-specific immune response enhancer. \ 18. The vaccine of claims 16 or 17 wherein the non-specific immune response enhancer is an adjuvant. 19. A method for inducing protective immunity in a patient, comprising administering to a patient a pharmaceutical composition according to any one of claims 9-11. 20. A method for inducing protective immunity in a patient, comprising administering to a patient a vaccine according to any one of claims 12-18. 21. A fusion protein comprising two or more polypeptides according to any one of claims 1-4. 22. A fusion protein comprising one or more polypeptides according to any one of claims 1-4 and ESAT-6. 23. A pharmaceutical composition comprising a fusion protein according to claim 21 or 22 and a physiologically acceptable carrier. 24. A vaccine comprising a fusion protein according to claims 21 or 22 and a non-specific immune response enhancer. 25. The vaccine of claim 24 wherein the non-specific immune response enhancer is an adjuvant. 26. A method for inducing protective immunity in a patient, comprising administering to a patient a pharmaceutical composition according to claim 23. 27. A method for inducing protective immunity in a patient, comprising administering to a patient a vaccine according to claims 24 or 25. 28. A method for detecting tuberculosis in a patient, comprising: (a) contacting dermal cells of a patient with one or more polypeptides according to any one of claims 1-4; and (b) detecting an immune response on the patient's skin and therefrom detecting tuberculosis in the patient. 29. A method for detecting tuberculosis in a patient, comprising: (a) contacting dermal cells of a patient with a polypeptide having an N- terminal sequence selected from the group consisting of sequences recited in SEQ ID NO: 134 and 135; and (b) detecting an immune response on the patient's skin and therefrom detecting tuberculosis in the patient. 30. A method for detecting tuberculosis in a patient, comprising: (a) contacting dermal cells of a patient with one or more polypeptides encoded by a DNA sequence selected from the group consisting of SEQ ID Nos.: 3, 11 and 12, the complements of said sequences, and DNA sequences that hybridize to a sequence recited in SEQ ID Nos.: 3, 11 and 12; and (b) detecting an immune response on the patient's skin and therefrom detecting tuberculosis in the patient. 31. The method of any one of claims 28-30 wherein the immune response is induration. 32. A diagnostic kit comprising: (a) a polypeptide according to any one of claims 1-4; and (b) apparatus sufficient to contact said polypeptide with the dermal cells of a patient. 33. A diagnostic kit comprising: (a) a polypeptide having an N-teπninal sequence selected from the group consisting of sequences recited in SEQ ID NO: 134 and 135; and (b) apparatus sufficient to contact said polypeptide with the dermal cells of a patient. 34. A diagnostic kit comprising: (a) a polypeptide encoded by a DNA sequence selected from the group consisting of SEQ ID Nos.: 3, 11 and 12, the complements of said sequences, and DNA sequences that hybridize to a sequence recited in SEQ ID Nos.: 3, 11 and 12; and (b) apparatus sufficient to contact said polypeptide with the dermal cells of a patient.

Inventors: CAMPOS-NETO ANTONIO, DILLON DAVIN C, HOUGHTON RAYMOND, REED STEVEN G, SKEIKY YASIR A W, TWARDZIK DANIEL R, VEDVICK THOMAS H, CAMPOS-NETO, ANTONIO, DILLON, DAVIN, C., HOUGHTON, RAYMOND, REED, STEVEN, G., SKEIKY, YASIR, A., W., TWARDZIK, DANIEL, R., VEDVICK, THOMAS, H.
Applicants: CORIXA CORP, CORIXA CORPORATION
Application year: 1996
Main classification: C12N15
IPC codes: A61K31, A61K38, A61K39, A61K48, A61P31, A61P37, C07K14, C12N1, C12N5, C12N15, C12Q1, G01N33