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Biomedical subjects

C S David

Publications and source records attributed to C S David.

At least 307 records · Page 17Linked to original sources
PubMed1979

Genetic control of immune response to sperm whale myoglobin in mice. II. T lymphocyte proliferative response to the synthetic antigenic sites.

The genetic control of T lymphocyte proliferative response to the five synthetic antigenic sites of myoglobin, two synthetic nonantigenic control peptides, and one "nonsense" peptide was determined in independent and recombinant strains of mice. In all the strains examined, the nonantigenic control peptides and the "nonsense" peptide did not invoke a response in myoglobin-primed mice. Further, when mice were not primed with whole myoglobin, no response was obtained with any of the antigenic sites. Haplotypes H-2d, H-2f, and H-2s are higher responders to sites 1 and 2, whereas haplotypes H-2d and H-2s are high responders to site 5. Response to site 3 may be controlled by a non-H-2-linked gene. Site 4 can stimulate H-2b and H-2k haplotypes that are nonresponders to the whole myoglobin. Studies with the recombinant strains suggested that Ir genes to sites 1 and 2 map in the I-A subregion and I-C subregion and were designated Ir-Mb-1,2(A) and Ir-Mb-1,2(C). Ir genes to sites 4 and 5 mapped only in the I-A subregion and were designated Ir-Mb-4(A) and Ir-Mb-5(A). These studies suggest that individual antigenic sites in a molecule are controlled by unique Ir genes.

Animals↗
PubMed1978

A new lymphocyte-activating determinant locus expressed on T cells, and mapping in I-C subregion.

A new lymphocyte-activating determinant (Lad) locus expressed on T cells was identified, mapping in the I-C subregions of H-2k and H-2d haplotypes. The mixed lymphocyte reaction stimulation could be inhibited by anti-Ia sera made in strains incompatible for this chromosomal segment. Experiments with purified lymphocyte cell populations suggested that this Lad locus was expressed on T cells. Further, only purified T cells were able to remove the inhibiting activity from the anti-Ia sera. I-C subregion gene(s) seem to code for products selectively expressed on a subpopulation of T cells.

Animals↗
PubMed1978

Inhibition of dual Ir gene-controlled T-lymphocyte proliferative response to poly (Glu56Lys35Phe9)n with anti-Ia antisera directed against products of either I-A or I-C subregion.

Previous studies have demonstrated that both the antibody and T-lymphocyte proliferative immune responses to poly(Glu53Lys36Phe11)n (GLphi) are under the control of two major histocompatibility-linked immune response (Ir) genes. One gene, termed Ir-GL phi-alpha, has been mapped to the I-C or I-E subregion of the major histocompatibility complex, while the other, termed Ir-GL phi-beta, has been mapped to the I-A subregion. In this paper we examine the effect of anti-I-region-associated (Ia) antisera on the T-lyphocyte proliferative response to GL phi. Antibodies directed against Ia antigens coded for by genes in either the I-A or I-C subregion were found to inhibit the proliferative response to GLphi. These results suggest that a function mediated by two Ir gene products can be blocked by anit-Ia antisera directed against either one, and thus, that both products are expressed on the cell surface.

Animals↗
PubMed1978

Immune response-associated antigens on mouse leukemia cells. II. Anti-Ia sera inhibit the MLR reaction between normal GR spleen cells and syngeneic spleen cells of GRSL tumor-bearing mice.

Mitomycin C-treated ascites cells of Ia antigen-positive GRSL14 tumor cells and spleen cells from GRSL14 tumor-bearing mice stimulated lymphocyte proliferative responses in normal syngeneic GR spleen cells. Furthermore, mitomycin C-treated T cells purified from spleen cells of tumor-bearing mice also stimulated normal GR spleen cells. Anti-Ia sera inhibited the stimulating ability of tumor cells and of spleen cells of tumor-bearing mice. These data suggest a role for I region gene products in immune surveillance for syngeneic tumors.

Animals↗
PubMed1978

Murine Ia antigens: identification and mapping of Ia.23 and further definition of the I-E subregion.

The Ia.23 specificity is a private specificity of the H-2d haplotype which we have assigned to the I-E subregion. It is found on the same Ia molecule that bears Ia.7, a public specificity previously assigned to the I-C subregion of haplotypes H-2d, H-2k, H-2p and H-2r. We suggest a reassignment of specificity Ia.7 to the I-E subregion to simplify the interpretation of the data presented in this paper and elsewhere, and to permit an orderly description of that part of the I region to the right of I-J.

Animals↗
PubMed1978

Structural studies of the protein portion of the H-2-linked Ia glycoprotein antigens of the mouse: tryptic peptide comparison of products from the I-A and I-C subregions of B10-HTT.

Ia antigens from the I-A8 and I-Ck subregions of the B10.HTT (H-2t3) strain of mice were isolated by indirect immunoprecipitation of arginine-labeled, nonionic detergent-solubilized materials. After biochemical purification the electrophoretically homogeneous 28,000 dalton glycoprotein beta chains from the Ia precipitates were digested with trypsin and the resultant radiolabeled tryptic peptides were compared by analytical ion exchange chromatography. These comparisons reveal that the beta chains of Ia antigens from the A (I-A8) and C (I-Ck) subregions of B10.HTT share only two out of 12 to 14 of their arginine tryptic peptides. Thus these noncross-reactive Ia antigens are structurally quite diverse, and would possess sufficient structural variability to account for their lack of antigenic cross-reactivity.

Amino Acids↗
PubMed1978

Genetic control of immune response to sperm whale myoglobin in mice. I. T lymphocyte proliferative response under H-2-linked Ir gene control.

Studies on the genetic control of immune response to sperm whale myoglobin were initiated. As demonstrated in this paper, the T lymphocyte proliferative response to whale myoglobin is under H-2-linked Ir gene control. Mice of H-2d, H-2f, and H-2s haplotypes were high responders to the myoglobin, whereas haplotypes H-2b, H-2k, H-2p, H-2q, and H-2r were low responders. The Ir gene(s) was localized between H-2K and H2D regions, since the recombinant strain A.TL (KsIkSkDd) was a low responder and A.TH (KsIsSsDd) was a high responder. Further studies with recombinant strains revealed that the expression of the high-responder I-Ad or Ias alleles was sufficient to give a good response, since strains D2.GD (d d b b b b b b) and B10.HTT (s s s s k k k d) were high responders. The expression of the I-Cd allele in strains B10.A (k k k k k d d d) and B10.A(5R) (b b b k k d d d) also gave high response, and thus suggested a second Ir gene, derived from the H-2d haplotype. The finding that expression of the I-Cs allele in B10.S(8R) (k k ? ? s s s s) did not result in high response suggests the lack of the second Ir gene in the high-responder H-2s haplotype.

Animals↗
PubMed1977

The role of gene products of the I-J subregion in mixed lymphocyte reactions.

We have examined the MLR reaction in two sets of recombinants that differ in the I-J subregion. In both cases, significant stimulation was mediated by antigens controlled by genes in the I-J subregion. This stimulation was inhibitable by the addition of the culture of antisera directed against the I-J gene products on the stimulator cell. The specificity of this inhibition was shown by specific blocking of the relevant gene product on F1 hybrid stimulator cells. MLR stimulation was also eliminated by pretreatment of the stimulator population with anti-I-J sera plus complement. Pretreatment of F1 hybrid stimulator T cells with anti-I-J sera directed against either parental I-J product in the presence of complement, completely eliminated stimulation, indicating that there is no allelic exclusion of the relevant I-J products. Pretreatment with an anti-I-E/I-C serum and complement also eliminated stimulation, suggesting that the stimulating T cells express both I-J and I-E/I-C subregion products. This assay offers a potentially more direct and practical method for serological detection of the I-J products.

Animals↗
PubMed1977

Properties of reticulum cell sarcomas in SJL/J mice. V. Nature of reticulum cell sarcoma surface antigen which induces proliferation of normal SJL/J T cells.

The results of studies on the reticulum cell sarcoma (RCS) tumors of SJL/J mice presented here, indicate that spontaneous tumors, which arise in older mice, also possess the capacity to induce the vigorous proliferative response in syngenetic T lymphocytes that are characteristic of the transplantable RCS lines. Analysis of cell surface antigens revealed the presence of Ia determinats on gradient-purified transplantable RCS tumor cells; however, these cells did not express Thy 1.2, nIg, or, any of the viral proteins that were tested for by specific antisera. Pretreatment of RCS cells with anti-Ia sera and complement-deleted cells that were stimulatory for syngenetic T lymphocytes, and addition of anti-Ia sera directly to cultures blocked the proliferative response at the stimulator (RCS) cell level. Lymph node cells from H-2(8) strains other than SJL/J, including A.SW and B10.S also gave proliferative responses to RCS cells, although lower in magnitude. A requirement on the part of responding cells for identity with RCS cells at the Ir region was indicated by the finding that A.TH but not A.TL lymph node cells responded to RCS. It is concluded that RCS cells stimulate Ir-region identical T cells (without evidence of presensitization) through a modification in the expression of Ia antigens on the surface of the tumor cells.

Animals↗
PubMed1977

Partial chemical characterization of Ia antigens derived from murine thymocytes.

Previous chemical studies attempting to demonstrate Ia antigens on mouse thymocytes have given contradictory results. We attempted to resolve the question of whether Ia antigens exist on thymocytes (defined as thymus cells that bear a T cell marker) by isolating strain C3H thymocytes free of other contaminating cells using the fluorescence-activated cell sorter, and then chemically testing the purified populations for Ia antigens. Immunoglobulin-negative thymus cells and thymus cells selected with a rabbit antiserum to mouse brain were the two populations of thymocytes labeled with [3H]leucine after sorting. Radiolabeled proteins were solubilized with the non-ionic detergent Nonidet P-40, reacted with anti-Ia antiserum, and analyzed by electrophoresis on discontinuous sodium dodecyl sulfate/polyacrylamide gels. Ia antigens were recovered from both cell populations. These antigens were synthesized by thymocytes and were found on molecules composed of two chains of molecular weight 33,000 and 25,000, respectively, similar to Ia antigens derived from spleen cells. Assuming that all thymocytes bear similar amounts of Ia antigens, we estimated that they have approximately 1/50 the amount of Ia antigens that spleen cells do.

Animals↗
PubMed1977

Reactivity of anti-HLA sera against mouse lymphocytes.

The reactivity of anti-HLA hyper-immune sera was tested by the microlymphocytotoxicity technique (LCT) against a panel of mouse lymphocytes. Three levels of reactivity were observed: negative (immune sera titre 1:20 or less), weak (titre 1:40 to 1:80 with a percentage of dead cells less than 50%) or strong (titre 1:60 or more with 100% killing). Thirteen normal human sera were non-reactive. Eleven out of 60 hyper-immune sera were strongly reactive. Tests using congenic lines showed that the reactivity was controlled at the H-2 complex. One serum (CODRON) was studied in detail. When tested against a panel of strains carrying 10 different H-2 haplotypes, it reacted strongly against lymphocytes H-2d, ja, k, p and r; and did not react, or at least only weakly, against lymphocytes H-2b, f, q, s and v. Tests using mouse strains carrying the recombinant H-2 haplotypes h4, i5, i, y2, g, g2 and t1, suggested that the observed reactivity was directed against structures controlled at the K end of the H-2 complex (H-2.47?). Absorption-elution experiments with human and murine lymphocytes and platelets confirmed that the structures recognised by serum CODRON were determined at the major histocompatibility complex.

Animals↗
PubMed1976

Properties of the antigen-specific suppressive T-cell factor in the regulation of antibody response of the mouse. IV. Special subregion assignment of the gene(s) that codes for the suppressive T-cell factor in the H-2 histocompatibility complex.

The locus of the gene that codes for the antigen-specific suppressive T-cell factor was determined to be in a new subregion "I-J" which locates between I-B and I-C subregions in the H-2 histocompatibility complex. This was shown by two different lines of evidence: (a) The absorbing capacity for the suppressive T-cell factor of several alloantisera against restricted I subregions did not correlate with their specificity for previously known Ia molecules which are coded for by genes in I-A and I-C subregions, but was associated with the specificity for the products of genes putatively present between I-B and I-C subregions. By the occurrence of special recombinant strains, i.e. B10.A(5R), B10.A(3R), B10.S(9R), and B10.HTT, which differ with respect to the I-J subregion, we were able to produce alloantisera which distinguish I-J subregion gene products. The absorption studies using these special alloantisera directed to I-J subregion clearly indicated that the suppressive T-cell factor is a product of I-J subregion gene(s), and that the molecule is distinct from known Ia molecules expressed on splenic B cells. (b) Taking advantage of the fact that there is a strict histocompatibility requirement for the effective suppression between the donor and recipient strains of the suppressive T-cell factor, we were able to determine the required identities of the genes in the H-2 complex existing among those present between I-B and I-C. Again, utilizing the T-cell factors obtained from special recombinant strains, i.e. B10.A(4R) and B10.A(5R), we were able to locate the gene that codes for the suppressive T-cell factor reactive only with relevant haplotype strains between I-B and I-C subregions. These results are most reasonably explained by the presence of a new subregion I-J which is specialized in coding for the suppressive T-cell factor as a different molecule from previously known Ia molecules.

Animals↗
PubMed1976

T lymphocyte-enriched murine peritoneal exudate cells. III. Inhibition of antigen-induced T lymphocyte Proliferation with anti-Ia antisera.

The recent development of a reliable murine T lymphocyte proliferation assay has facilitated the study of T lymphocyte function in vitro. In this paper, the effect of anti-histocompatibility antisera on the proliferative response was investigated. The continuous presence of anti-Ia antisera in the cultures was found to inhibit the responses to the antigens poly (Glu58 Lys38 Tyr4) [GLT], poly (Tyr, Glu) ploy D,L Ala-poly Lys [(T,G)-A--L], poly (Phe, Glu)-poly D,L Ala-poly Lys [(phi, G)-A--L], lactate dehydrogenase H4, staphylococcal nuclease, and the IgA myeloma protein, TEPC 15. The T lymphocyte proliferative responses to all of these antigens have previously been shown to be under the genetic control of major histocompatibility-linked immune response genes. The anti-Ia antisera were also capable of inhibiting proliferative responses to antigens such as PPD, to which all strains respond. In contrast, antisera directed solely against H-2K or H-2D antigens did not give significant inhibition. Anti-Ia antisera capable of reacting with antigens coded for by genetically defined subregions of the I locus were capable of completely inhibiting the proliferative response. In the two cases studied, GLT and (T,G)-A--L, an Ir gene controlling the T lymphocyte proliferative response to the antigen had been previously mapped to the same subregion as that which coded for the Ia antigens recognized by the blocking antisera. Finally, in F1 hybrids between responder and nonresponder strains, the anti-Ia antisera showed haplotype-specific inhibition. That is, anti-Ia antisera directed against the responder haplotype could completely block the antigen response controlled by Ir genes of that haplotype; anti-Ia antisera directed against Ia antigens of the nonresponder haplotype gave only partial or no inhibition. Since this selective inhibition was reciprocal depending on which antigen was used, it suggested that the mechanism of anti-Ia antisera inhibition was not cell killing or a nonspecific turning off of the cell but rather a blockade of antigen stimulation at the cell surface. Furthermore, the selective inhibition demonstrates a phenotypic linkage between Ir gene products and Ia antigens at the cell surface. These results, coupled with the known genetic linkage of Ir genes and the genes coding for Ia antigens, suggest that Ia antigens are determinants on Ir gene products.

Animals↗