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Biomedical subjects

C S David

Publications and source records attributed to C S David.

At least 253 records · Page 14Linked to original sources
PubMed1982

Growth of SJL/J-derived RCS as related to its ability to induce T cell proliferation in the host. II. Negative influence of H-2d1.

Backcross SJL x (SJL x BALB/c)F1 and (SJL x BSVS)F1 mice were examined for their ability to support growth of transplantable SJL lymphoma (reticulum cell sarcoma (RCS). A marked linkage to H-2 was noted in that H-2s/d backcross mice failed to support tumor growth, while H-2s/s backcross mice showed approximately 70% of the growth seen in SJL mice, as judged by lymph node and spleen weights. Spleen cells obtained from backcross mice by splenectomy were examined for their ability to give proliferative responses to gamma-RCS cells, whereafter individual splenectomized mice were also examined for their ability to support lymphoma growth. Both properties showed a similar degree of linkage to H-2 and to each other, although there seemed to be a segregating non-H-2 BALB gene which also exerted an additional, less marked negative influence on the proliferative responses. It is suggested that the proliferative response in vivo may contribute to the lymphoma growth and that the presence of H-2d is inhibitory. (SJL x BSVS)F1 mice gave excellent proliferative responses and supported growth of RCS to approximately 80% of those of controls. These results confirm previous conclusions on the negative effect of H-21d in F1 hybrids on both phenomena.

Animals↗
PubMed1982

Ia antigens are the stimulating determinants in the syngeneic mixed lymphocyte reaction.

The murine syngeneic mixed lymphocyte reaction (sMLR) is a T cell proliferative response to self-antigens on non-T stimulator cells. The nature and specificity of the stimulating antigens was investigated using secondary MLR. Lymph node cells were stimulated in vitro by syngeneic spleen cells. After optimal proliferation occurred, the responding cell population was recovered and restimulated with spleen cells from mice of various haplotypes. The secondary response was found to be specific for the haplotype of the primary stimulator (a self-restricted response). The use of recombinant mice in the secondary stimulation localized the determinant to the I-A and/or I-E subregions of the major histocompatibility complex (MHC). This result was confirmed by the ability of monoclonal antibodies directed to the I-A or I-E subregion products to significantly inhibit the response while alloantiserum directed to products of the K or D regions had no effect.

Animals↗
PubMed1982

Molecular specificity of a monoclonal anti-Ik alloantibody identifying a highly conserved determinant on mouse I-A, I-E and human DR antigens.

We have investigated, using serological and biochemical assays, the specificity of an A.TH anti-A.TL-derived monoclonal antibody (mAb), designated 40.B, directed at a highly conserved antigenic determinant expressed on the majority of murine and human MHC class II antigens. In the mouse, mAb 40.B defines a new specificity expressed on the Ia products of the H-2 haplotypes K, d, b, v, r, p, u, j and w3. Analysis of its reactivity with H-2 recombinant strains and the results of the competitive binding inhibition of 125I-labeled mAb 40.B to B10.BR cells with I-Ak and I-Ek specific mAb suggested recognition of a shared Ia determinant expressed on both I-Ak and I-Ek molecules. This has been confirmed by sequential immunoprecipitation studies which demonstrated the specificity of mAb 40.B for the Ak beta Ak alpha, Ab beta Ab alpha, Ad beta Ad alpha, Ek beta Ek alpha, Es beta Ek beta and Ed beta Ed alpha dimers. In humans, this mAb bound to and immunoprecipitated HLA-D/DR molecules expressed on lymphoblastoid cell lines carrying the MT1 and MT2 supertypic specificities. The possible implications of these findings with regard to an evolutionary model of MHC class II antigens are discussed.

Animals↗
PubMed1982

Genetic control of the immune response to haemoglobin. IV. Ly-1+ T-cells and appropriate non-H-2 genes are required for in vitro responses to alpha- and beta-subunits of human adult haemoglobin.

Experiments were conducted to determine if non-H2 gene effects could be demonstrated in mice which had been primed to either the alpha-subunit or beta-subunit of human haemoglobin. It was found that C3H.SW (H-2b) and Balb/c (H-2d) mice are low responder mice to alpha-chain of a haemoglobin when compared to H-2 identical B10 (H-2b) and B10.D2(H-2d) mice. B120.S and A.SW (both H-2s) are responsive to beta-chain challenge while Balb/c mice are low responders in contrast to high responder B10.D2 mice. Ly-1+ cells were demonstrated to be required (by cell depletion experiments) for an in vitro T-cell proliferative response to either subunit. In these experiments, Ly-2+ cells were not of crucial importance.

Animals↗
PubMed1982

Regulation of experimental autoimmune thyroiditis: influence of non-H-2 genes.

Experiments were conducted to investigate the non-H-2 genetic effects on experimental autoimmune thyroiditis (EAT). Strains having C3H or BALB background in general produced higher autoimmune responses to mouse thyroglobulin (MTg) than the B10 or A strains. Comparisons of C3H and B10 congenic strains carrying similar H-2 haplotypes demonstrated that the C3H congenics had significantly higher MTg antibody titres and more severe thyroid damage, even when the strains carry the low responder H-2 haplotypes. These observations show that non-H-2 gene(s) influences EAT, in addition to genes in the MHC.

Animals↗
PubMed1982

Genetic control of experimental autoimmune myasthenia gravis in mice. III. Ia molecules mediate cellular immune responsiveness to acetylcholine receptors.

When MHC congenic and recombinant mice are inoculated with Torpedo acetylcholine receptors (AChR) with adjuvants, the magnitude of autoantibody responses to muscle AChR and the defect of neuromuscular transmission closely parallel in vitro lymphocyte proliferative responses to Torpedo AChR. All of these responses are controlled by gene(s) at the I-A subregion of the H-2 complex. Data presented in this report confirm in back-cross mice that T lymphocyte proliferative responses to AChR are controlled by a Mendelian dominant gene linked to H-2, at the I-A subregion. Lymphocyte responses were eliminated by blocking Ia antigens on lymph node cell surfaces with appropriate anti-I-A alloantisera and by removal of adherent cells. A spontaneous mutation at the I-A subregion in the B6 strain, which resulted in structural alteration of the A beta chain of Ia, converted high responsiveness to AChR to a state of low responsiveness. These data implicate a macrophage-associated Ia molecule in induction of autoimmune responses to AchR, probably in the presentation of AChR to helper T lymphocytes that thereby help B lymphocytes to differentiate into anti-AChR antibody-forming cells.

Animals↗
PubMed1981

Type II collagen-induced arthritis in mice. I. Major histocompatibility complex (I region) linkage and antibody correlates.

A model of arthritis was established by the injection of type II collagen into mice. Only mice bearing the H-2q haplotype were susceptible to the disease. Susceptibility was further mapped by the use of recombinant strains on the Iq locus. Type II collagen arthritis was observed in the (resistant X susceptible) F1 cross. Mice strains were designated high, intermediate, or low responders with respect to the anti-type II antibody levels measured by radioimmunoassay. Arthritis-susceptible strains were all classified as high antibody responders. The clinical and histological appearance of type II collagen arthritis in the mouse indicates that it may be a good animal model for the investigation of various immunogenetic traits in rheumatoid arthritis.

Animals↗
PubMed1981

Hybrid (combinatorial) Ia specificities: gene complementations to generate Ia.22.

Ia specificity 22 is expressed on a hybrid I-E molecule formed by the association of a beta chain (Ae) coded for by the I-A subregion and an alpha chain (E alpha) encoded by the I-E subregion. Ia.22 can be generated by the complementation of Ab, Ak, As, Ar, with Ed, Ek, Ep, Er, Ew3, Eu, Ev but Eb, Ef, Eq, and Es. With the exception of H-2p which does not complement with As to generate Ia.22, all Ia. 7-positive (I-E) haplotypes can provide the permissive E alpha allele. It is postulated that Ia.22 is a combinatorial Ia determinant generated by the association of the alpha and beta chains. These determinants are probably involved in the immune recognition of antigens under dual Ir-gene control.

Animals↗
PubMed1981

Reconstitution of Ir genes, Ia antigens, and mixed lymphocyte reaction determinants by gene complementation.

By using clones of murine T cells reactive with alloantigens as well as soluble antigens, it has been possible to demonstrate that Ia antigens, Ir gene phenomena (defined as the ability of immune T cells to recognize antigen), and mixed lymphocyte reaction (MLR)-stimulating determinants encoded within the I-A subregion are different manifestations associated with same product. These studies utilized the I-Ab mutant mouse B6.C-H-2bm (bm12), whose defect in the normal expression of the cell surface products of the I-Ab subregion can be partially circumvented through trans-complementation by deriving hybrids between bm12 and mice expressing normal I-A subregion products. Such mice [e.g., (bm12 X B10.A)F1] express several serologically normal I-Ab products but have defects in certain I-A subregion gene products normally expressed on cells of H-2a X H-2b heterozygote mice that are used as restricting elements for antigen recognition by antigen-reactive T cell clones or recognized as alloantigens by alloreactive T cell clones. This defect in cell surface expression of certain normal I-Ab products on the mutant bm12 cells has allowed us to suggest that there exist trans-complementing products on H-2a X H-2b heterozygote mice consisting of Ab alpha Ak beta and Ak alpha Ab beta that restrict antigen recognition by cloned T cells, stimulate MLR responses by cloned T cells, and react with certain anti-Ia antisera.

Animals↗
PubMed1981

Serological and biochemical analysis of Ia molecules in the I-A mutant B6.C-H-2.

Strain B6.C-H-2bm12 has a mutation in the I-A subregion of the mouse H-2 gene complex, which causes skin graft rejection, mixed lymphocyte reaction (MLR), and alterations in the expression of Ia antigens. The mutation affects the expression of Ia.3, 8, 9, 15, and 20 on normal spleen cells. When the spleen cells were stimulated with lipopolysaccharide (LPS), the expression of all Ia specificities were found except Ia.8. Ia molecules when internally labeled with 3H-leucine can be precipitated with antisera directed against Ia.3, 9, 15, and 20, but not Ia.8. When F1s are made between the mutant bm12 and unrelated haplotypes, Ia.3, 9, 15 and 20 can be detected by microcytotoxic assay on normal spleen cells, but not Ia.8. These studies suggest: (1) The mutation affects either the amount of Ia molecules expressed on normal spleen cell surfaces or the molecule is anchored improperly in the cell surface such that it is not accessible for cytotoxicity and radioiodination. (2) Specificity Ia.8, which may be a combinatorial determinant, is absent in the mutant because of a structural alteration in one of the chains, probably the beta chain. (3) The mutation does not involve the Ae chain. The significance of this finding in relation to I region-mediated allorecognition and antigen presentation is discussed.

Animals↗
PubMed1981

Genetic control of the immune response to haemoglobin. I. Demonstration of separate genetic control of the responses to the alpha- and beta-subunits by in vitro lymphocyte proliferation.

These studies were undertaken to analyse the genetic control of the immune response to an oligomeric protein and the role of individual subunits in the regulation of the response. Human adult haemoglobin (Hb) was selected as a model for these studies because it is a well-characterized protein and its antigenic structure is being determined in our laboratories. Mice of various congenic strains were immunized with Hb and the lymph node cells from Hb-primed mice were challenged in vitro with Hb, and its alpha-chain and beta-chains as well as an appropriate control antigen. Lymphocyte proliferation was determined by 3H-thymidine incorporation. The data collected indicated that mice of the H-2b and H-2d haplotypes were high responders while H-2k, H-2s, H-2q and H-2j haplotype mice were low responders to Hb. Studies with H-2 recombinant strains indicated that the immune response to Hb and its subunits is determined by genes in the I-A subregion and the D end of the H-2 complex. The significance of these findings in terms of control and regulation of the overall response to native Hb are discussed.

Animals↗