bluuebunny/crossref_metadata_2025_split huggingface dataset:
The anti-DNA-associated idiotype 8.12 is encoded by the V lambda II gene family and maps to the vicinity of L chain CDR1.
Authors: Paul E , Iliev A A , Livneh A , Diamond B 
Published: December 2022

Abstract
The 8.12 idiotype is an anti-DNA-associated Id present on lambda L chains that are expressed at high titers in 50% of patients with systemic lupus erythematosus. Since this Id can be present on as much as a third of a patient's anti-DNA antibodies and is found in renal glomeruli, 8.12 is thought to be a marker for a subset of pathogenic anti-DNA auto-antibodies. A molecular analysis of the 8.12 positive antibodies was designed to explore the genetic basis of this Id. Monoclonal human B cell lines were generated by transformation with EBV and lambda L chain-secreting lines were analyzed for Id expression and V region gene usage. In this panel of Ig lambda cell lines, the 8.12 idiotype is encoded exclusively by members of the V lambda II gene family. The sequences of several 8.12+ and 8.12- V lambda II genes are reported here and are used to map the 8.12 Id to the vicinity of CDR1, as well as to further characterize the large and polymorphic V lambda II gene family.
Biochemical specificity of H-2M3a. Stereospecificity and space-filling requirements at position 1 maintain N-formyl peptide binding.
Authors: Vyas J M , Shawar S M , Rodgers J R , Cook R G , Rich R R 
Published: December 2022

Abstract
The maternally transmitted Ag is a cell surface product of three gene products: 1) H-2M3a (formerly Hmta), a class I MHC heavy chain; 2) beta 2-microglobulin; and 3) maternally transmitted factor (Mtf), the N-terminus of the mitochondrially encoded ND1 subunit of the reduced form of nicotinamide-adenine dinucleotide dehydrogenase. This class I molecule has been shown to be an N-formyl peptide receptor. Although the N-formyl moiety is necessary for binding to M3a, it is not sufficient. We proposed that the R group of the amino acid in position 1 plays a pivotal role in peptide binding to M3a. To test this hypothesis, analogues differing in size and stereospecificity of the R group were synthesized. Substitutions with other hydrophobic amino acids such as N-formyl phenylalanine and N-formyl valine had no significant effect on the ability of these Mtf alpha analogues to sensitize target cells (M3a, Mtf beta) to M3a, Mtf alpha-specific CTL. In contrast, the nonsubstituted, N-formylated, and N-acetylated glycyl analogues of Mtf beta bound equivalently to M3a in a peptide competition assay. Moreover, the alanine analogue bound in an N-formyl-dependent manner. To determine the limitations of the putative N-formyl pocket, peptide analogues were constructed incorporating D-isomer amino acids. When formylated D-alanine or D-methionine replaced the native methionine, these peptide derivatives did not show significant binding to M3a. Therefore, the presence of a space-filling R group (greater than hydrogen) is necessary for an antigenic peptide to bind M3a in an N-formyl-dependent manner. Additionally, the ability of M3a to discriminate between the optical forms of methionine and alanine demonstrates that this N-formyl pocket is stereospecific in its ability to bind peptide. Thus, we have defined three requirements for peptide binding to M3a: an N-formyl moiety at the amino terminus of the peptide, a space-filling R group at position 1 to maintain this N-formyl specificity, and the correct stereoisomer of the first amino acid.
Protection of mice and nude rats against toxoplasmosis by a multiple antigenic peptide construction derived from Toxoplasma gondii P30 antigen.
Authors: Darcy F , Maes P , Gras-Masse H , Auriault C , Bossus M , Deslee D , Godard I , Cesbron M F , Tartar A , Capron A 
Published: December 2022

Abstract
The first part of this work presents the sequence of the first 20 NH2 terminus residues obtained from P30, the major surface Ag of Toxoplasma gondii, purified by HPLC. A synthetic peptide (P30 48-67) has been prepared both in linear form and as a multiple antigenic peptide (MAP) construct. Immunization of mice and rats with the P30 48-67 MAP in the presence of IFA induces high levels of IgG antibodies that recognize both the linear peptide and the MAP construct in ELISA, and P30 in Western blots of NP-40-extracted tachyzoite Ag. Because these sera are negative in immunofluorescence assays with whole tachyzoites, it seems that IgG antibodies induced by P30 48-67 MAP, although recognizing the denatured structure, are unable to recognize the native protein. However, the protective effect of both constructs has then been studied in mice and nude rats. Whereas immunization of mice with the monomeric peptide does not confer any protection against oral infection with 1200 cysts of T. gondii 76K strain (mortality within 11 days), 40% of mice immunized with the MAP construct survived up to 75 days after infection. Nude rats were passively transferred with 5 x 10(4) T lymphocytes from P30 48-67 MAP-immunized Fischer rats before infection with 5 x 10(4) RH strain tachyzoites. They survived up to 40 days after infection and raised an intense IgG antibody response against P30, whereas nude rats transferred with control lymphocytes died within 21 days. This shows that immunization with P30 48-67 MAP also induces an efficient T cell immune response. The present work confirms the recently demonstrated role of P30 in protective immunity and shows the interest of peptide octameric constructions as inducers of partially protective immune responses in toxoplasmosis, as already demonstrated in schistosomiasis.
Application of a filamentous phage pVIII fusion protein system suitable for efficient production, screening, and mutagenesis of F(ab) antibody fragments.
Authors: Huse W D , Stinchcombe T J , Glaser S M , Starr L , MacLean M , Hellström K E , Hellström I , Yelton D E 
Published: December 2022

Abstract
We describe the application of a novel filamentous phage vector system suitable for efficient screening and production of F(ab) antibody fragments. The vector system can concurrently produce free F(ab) fragments and F(ab) displayed on the surface of M13 bacteriophage via a VHCH1-pVIII fusion protein. When expressed in a supO (nonsuppressor) strain of Escherichia coli free F(ab) can be produced. Antibody F(ab) fragments are secreted into culture medium at concentrations up to 0.3 mg/liter and conveniently subjected to detailed analysis with little or no purification. Higher concentrations of F(ab) (approximately 10 mg/liter) were found to accumulate in the periplasmic space. In this report the vector system is shown to produce correctly folded and assembled F(ab) fragments of chimeric L6, a mAb against a tumor-associated Ag expressed by many human carcinomas.
Effect of Haemophilus influenzae polysaccharide outer membrane protein complex conjugate vaccine on macrophages.
Authors: Ambrosino D M , Bolon D , Collard H , Van Etten R , Kanchana M V , Finberg R W 
Published: December 2022

Abstract
Haemophilus influenzae type b polysaccharide-conjugate vaccines elicit protective antibody responses in young infants. One of these conjugates, polysaccharide linked to outer membrane protein complex (PRP-OMPC), is produced by linking the capsular polysaccharide to an outer membrane protein complex derived from group B Neisseria meningitidis. The outer membrane protein complex contains T cell carrier epitopes that elicit T cell-dependent antibody responses. OMPC also has been shown to increase the antibody response to other proteins administered concurrently that are not covalently linked (i.e., acts as an adjuvant). In this study PRP-OMPC immunized mice demonstrated significant increases in spleen size as well as in splenocyte number as compared to saline controls (p &lt; 0.01, p &lt; 0.001, respectively). No such increase was noted after immunization with another H. influenzae type b-conjugate vaccine, oligosaccharide linked to a variant of diphtheria toxin. By analytic flow cytometry, the mice immunized with PRP-OMPC demonstrated an increase in large splenocytes expressing the Ag Mac-1 (CD11b, CR3). Furthermore, the spleens on histologic examination were characterized by an increase in the red pulp area consisting predominantly of cells of macrophage morphology. By immunohistochemical staining, the cells were identified as macrophages due to expression of Mac-1 and p150,95 (CD11C) Ag. After PRP-OMPC immunization, severe combined immunodeficient mice also demonstrated significant splenomegaly with an increase in macrophages identified by expression of Mac-1 and MHC class II Ag. Thus PRP-OMPC vaccine resulted in T cell-independent splenomegaly with an increase number of macrophages. We propose that this unique property may confer increased immunogenicity to PRP-OMPC through macrophage activation and cytokine release. Furthermore, the effect on macrophages may explain the "adjuvant" capacity of OMPC.
Regulation of the respiratory burst by cyclic 3',5'-AMP, an association with inhibition of arachidonic acid release.
Authors: Nielson C P , Bayer C , Hodson S , Hadjokas N 
Published: December 2022

Abstract
The mechanism of cAMP regulation of the respiratory burst was studied with HL-60 cells that had been DMSO-differentiated to a neutrophil-like cell. To evaluate the effects of known cAMP concentrations, cells were permeabilized with streptolysin-O. Chemotactic peptide (FMLP)-stimulated NADPH oxidase activity was inhibited by cAMP at concentrations higher than 3 microM. Because intracellular calcium was buffered, inhibitory actions of cAMP were not mediated by modulation of calcium concentration. Effects of cAMP on chemotactic peptide signal transduction mediated by phospholipase C, phospholipase D, and phospholipase A2 were then determined. Neither inositol phosphate generation (phospholipase C) nor phosphatidylethanol generation (phospholipase D activity in presence of 1.6% ethanol) induced by FMLP were significantly affected by cAMP. In contrast, cAMP potently inhibited FMLP-induced arachidonic acid mobilization (phospholipase A2). NADPH oxidase activity induced by exogenous arachidonic acid was not inhibited by cAMP. These results indicate that cAMP-mediated inhibition of arachidonic acid mobilization may be important in regulation of the respiratory burst.
Lipopolysaccharide increases glucocorticoid receptor expression in murine macrophages. A possible mechanism for glucocorticoid-mediated suppression of endotoxicity.
Authors: Salkowski C A , Vogel S N 
Published: December 2022

Abstract
In a previous study we demonstrated that IFN-gamma induced an increase in the number of glucocorticoid receptors (GR) in murine macrophages. To examine further the environmental signals involved in regulation of macrophage GR availability, we asked whether another classical macrophage-activating factor, LPS, would induce an increase in GR number in the macrophage cell line, RAW 264.7, and in primary macrophages from C3H mice. We report that treatment of RAW 264.7 cells and peritoneal exudate macrophages from C3H/OuJ mice with protein-free, phenol water-extracted LPS (PW-LPS) induced an increase in the number of GR. A significant increase in GR number was observed as early as 4 h after PW-LPS treatment, was maximal at 12 h, and remained heightened through 48 h. Optimal induction of the GR by PW-LPS was observed when murine macrophages were treated with 10 ng/ml of PW-LPS. The LPS-induced increase in macrophage GR number could be inhibited by polymyxin B. Macrophages obtained from the LPS hyporesponsive C3H/HeJ strain did not respond to PW-LPS, but did respond to protein-rich, butanol-extracted LPS with a modest increase in GR number after treatment with 2 micrograms/ml. Moreover, taxol, an antineoplastic agent with LPS mimetic activity, also increased GR number in murine macrophages. These results suggest that LPS is not only an important macrophage-activating signal, but may also be important in sensitizing the cell for negative regulatory events such as feedback inhibition by glucocorticoids.
IFN-gamma receptor-Ig fusion proteins. Half-life, immunogenicity, and in vivo activity.
Authors: Kürschner C , Ozmen L , Garotta G , Dembic Z 
Published: December 2022

Abstract
Two mouse IFN-gamma receptor (MoIFN gamma R)-Ig fusion proteins, which were constructed for the purpose of creating new efficient mouse IFN-gamma (MoIFN-gamma) inhibitor molecules, were studied in vivo to determine their plasma half-life and immunogenicity, and to show their biologic activity. The hybrid proteins show 40-h blood persistency. They do not provoke an antibody response when injected into mice, and they are biologically active in vivo, as demonstrated by the prevention of streptozotocin-induced diabetes. The two fusion proteins are efficient MoIFN-gamma antagonists and can be used in mouse models of human diseases to investigate the role of MoIFN gamma in these pathologic states.
Identification of a thyroiditogenic sequence within the thyroglobulin molecule.
Authors: Chronopoulou E , Carayanniotis G 
Published: December 2022

Abstract
Thyroglobulin (Tg)-specific T cells are important in the induction of experimental autoimmune thyroiditis (EAT), but the nature and the number of the Tg T cell epitopes involved in the disease process are unknown. Through the use of computerized algorithms that search for putative T cell epitopes, a 17-mer peptide (TgP1) was identified within the known portion of the rat Tg sequence (corresponding to amino acids 2495 to 2511 of the human Tg sequence) that induced strong mononuclear cell infiltration of the thyroid in classic EAT-susceptible murine strains such as SJL, C3H, and B10.BR and low or undetectable infiltration in EAT-resistant strains such as BALB/c and B10. TgP1 appears to be phylogenetically conserved since it is completely homologous to its bovine counterpart and differs at a single amino acid position from its human analogue. After priming with TgP1 in vivo, significant proliferative T cell responses to TgP1 in vitro were observed only with lymphocytes from susceptible (high responder) strains, thus correlating proliferative capacity with EAT induction. TgP1-primed T cells did not respond to intact mouse Tg (MTg) or rat Tg in vitro and, conversely, T cells primed in vivo with MTg or rat Tg did not respond to TgP1 in culture, suggesting that TgP1 is comprised of non-immunodominant T cell determinants. TgP1 was defined as a serologically nonimmunodominant epitope as well, since in vivo priming of all strains with MTg led to strong MTg-specific IgG responses but no TgP1-specific responses in ELISA assays. This was not due to lack of immunogenic B cell determinants on TgP1, however, because peptide challenge of EAT-susceptible strains elicited TgP1-specific IgG that also cross-reacted with MTg and rat, human, bovine, and porcine Tg. The data demonstrate that TgP1 delineates nonimmunodominant but highly immunogenic determinants at both the T and B cell level, which may play an important role in the development of autoimmune thyroiditis.
Evidence for the existence of two parallel differentiation pathways in the thymus of MRL lpr/lpr mice.
Authors: Matsuzaki Y , Pannetien C , Kanagawa O , Gachelin G , Nakauchi H 
Published: December 2022

Abstract
MRL mice homozygous for the lpr/lpr gene develop a massive lymphadenopathy caused by the accumulation of CD4-CD8-, Thy-1-positive T cells that express B220. This phenotypically unusual T cell population coexists with normal, B220- T cells in lpr/lpr animals. To investigate the origin and differentiation pathway of B220+ T cells, the expression of a panel of developmentally regulated cell surface markers including TCR, CD4, CD8, Thy-1, and B220 was examined. Thymocytes and peripheral T lymphocytes from lpr/lpr mice were analyzed by four-color flow cytometry. The results showed that both B220+ and B220- thymocytes contained all of CD4-CD8-, CD4+CD8+, and CD4 or CD8 single positive T cell subpopulation in the lpr thymus. Expression of the V beta 11 TCR, measured by flow cytometry and reverse polymerase chain reaction, was demonstrated in lpr thymus. However, the number of T cells expressing V beta 11 was greatly reduced in both the B220+ and B220- T cell populations in lymph node, spleen, and liver. Taken together, the data provide evidence for maturation and selection of a distinct population of B220+ T cells in the thymus of MRL lpr/lpr mice.
Novel human autoantibodies reactive with 5'-terminal trimethylguanosine cap structures of U small nuclear RNA.
Authors: Okano Y , Medsger T A 
Published: December 2022

Abstract
A class of RNA-containing particles, U small nuclear/nucleolar ribonucleoprotein particles (U snRNP), are well known to be targets for sera from patients with various autoimmune diseases. In the most cases the protein components carry the antigenic determinants. We have identified serum autoantibodies from three patients with systemic sclerosis that were directed against U1-U5 snRNA by immunoprecipitation of deproteinized 32PO4 labeled HeLa cell total RNA. By competitive radioimmunoprecipitation assays, an experimentally induced anti-2,2,7-trimethylguanosine (TMG) cap structure mAb inhibited the reaction of these antisera. In addition, IgG isolated from the antisera inhibited the anti-TMG mAb reaction to the U snRNA. Furthermore, a structural analog, 7-methylguanosine-triphosphate, competitively inhibited the reaction of the antisera to the U snRNA. Thus we concluded that the TMG cap structure of the U snRNA could be a target for serum autoantibodies.
Selective breeding of miniature swine leads to an increased rate of acceptance of MHC-identical, but not of class I-disparate, renal allografts.
Authors: Rosengard B R , Ojikutu C A , Fishbein J , Kortz E O , Sachs D H 
Published: December 2022

Abstract
Previous work from this laboratory demonstrated that tolerance to MHC-identical or class I-disparate renal allografts develops in approximately one third of miniature swine without exogenous immunosuppression. A back-cross study indicated that rejection of MHC-identical transplants due to minor Ag was controlled by one or possibly two non-MHC-linked, autosomal dominant Ir genes. According to this hypothesis, and assuming complete penetrance, graft acceptors would be homozygous recessive at the relevant Ir loci, as would their offspring. Alternatively, if the gene(s) were incompletely penetrant, then two acceptors could give rise to a rejector. However, a high rate of MHC-identical graft acceptance would still be expected in the offspring of acceptors even if the Ir gene(s) were incompletely penetrant. To test this hypothesis and to obtain a higher frequency of acceptor animals for studies of tolerance, a program of selective breeding of renal allograft acceptors was begun. In the present paper, we assess the effect of selective breeding on renal graft acceptance. The analysis indicates a marked increase in the rate of MHC-identical graft acceptance, from 27.3% (n = 24) for the earliest of the four chronologic subgroups assessed to 64.5% (n = 33) for the most recent subgroup (p less than 0.0001). Calculations of kinship revealed that the increased acceptance of MHC-identical grafts was not the result of differences between acceptors and rejectors in donor/recipient consanguinity. Class I-disparate grafts (n = 128) were similarly stratified chronologically and compared. Unlike MHC-identical grafts, the rate of acceptance of class I-disparate grafts has not changed over time. We conclude that rejector/acceptor status with respect to class I MHC incompatibility is determined by genetic factors in addition to those that control responses to minor antigen incompatibilities only.
Shedding of the CD44 adhesion molecule from leukocytes induced by anti-CD44 monoclonal antibody simulating the effect of a natural receptor ligand.
Authors: Bazil V , Horejsí V 
Published: December 2022

Abstract
The CD44 adhesion molecule, playing an important role in leukocyte extravasation, was down-regulated by PMA and ionomycin on granulocytes and by an immobilized or soluble anti-CD44 mAb both on granulocytes and lymphocytes. Soluble labeled CD44 molecules of lower apparent molecular mass as compared to their membrane counterparts were isolated from culture supernatants of stimulated surface iodinated cells. Shedding rather than internalization is the mechanism found to be responsible for the loss of CD44 from the cell surface. The size of the soluble CD44 shed from the cells stimulated in vitro corresponds to soluble CD44 isolated from human serum. These data suggest that shedding, induced by anti-CD44 antibody simulating the effect of a natural CD44 ligand, is an important regulatory mechanism controlling surface CD44 expression on leukocytes in vivo.
MHC class II deletion mutant expresses normal levels of transgene encoded class II molecules that have abnormal conformation and impaired antigen presentation ability.
Authors: Ceman S , Rudersdorf R , Long E O , Demars R 
Published: December 2022

Abstract
Successive transfers of HLA-DR alpha and beta genes restored expression of HLA-DR antigens to human B-lymphoblastoid cell line, LCL .174, from which all known expressible class II genes are deleted. While transferent cells displayed large amounts of DR on their surfaces, transgene-encoded DR3 molecules lacked a conformation-dependent epitope. DR1-restricted CTL lysis of DR1-expressing transferents pulsed with native influenza virus proteins was greatly reduced; the same cells were efficiently lysed in the presence of CTL-recognized influenza peptides. The properties of DR-expressing transferents of .174 suggest they are defective in producing peptides from exogenous proteins or in forming DR/peptide complexes. Comparison with other DR-expressing deletion mutants indicates that at least one gene in an approximately 230 kb DNA segment between the DQ1 and Ring 7 loci is needed for normal DR-mediated processing and presentation. Production of DR3 molecules having the conformation-dependent 16.23 epitope and efficient DR1-restricted presentation of influenza viral epitopes occurred in a B cell line that has a mutation specifically eliminating expression of the TAP1 transporter gene, which is in the approximately 230 kb interval and is needed for production of HLA class I/peptide complexes.
Expression, molecular association, and functions of C3 complement receptors CR1 (CD35) and CR2 (CD21) on the human T cell line HPB-ALL.
Authors: Delibrias C C , Fischer E , Bismuth G , Kazatchkine M D 
Published: December 2022

Abstract
We have investigated the expression, molecular association, ligand binding properties, and ability to transduce intracellular signals of CR1 and CR2 C3 receptors on cells of the human HPB-ALL T cell line. CR1 and CR2 on HPB-ALL cells bound polymeric C3b and C3dg and several anti-CR1 and anti-CR2 mAb recognizing different epitopes of the receptors on normal peripheral blood cells. Immunoprecipitated CR1 and CR2 exhibited similar m.w. to those of the receptors on normal peripheral blood T and B lymphocytes. CR1 and CR2 were partially associated in the form of CR1/CR2 complexes in the cell membrane as assessed by the ability of the receptors to cocap and cointernalize and to form a detergent-sensitive complex upon immunoprecipitation analysis. Triggering of CR2 with mAb OKB7 that recognizes an epitope associated with the ligand binding site of the receptor induced an increase in intracellular free calcium concentration in HPB-ALL cells. The signal provided by mAb OKB7 did not synergize with that triggered by anti-CD3 mAb UCHT1. Triggering of CR1 did not result in changes in intracellular free calcium concentration. Our observations have significance for the biology of normal human T cells because the majority of peripheral blood T cells that express CR1 also expressed CR2 and because a change in (Ca2+)i was induced by mAb OKB7 in purified normal T cells. These functions may be relevant for the regulatory role of C3 fragments on the immune response to T-dependent Ag and for the penetration into T cells of lymphocytotropic viruses.