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C S David

Publications and source records attributed to C S David.

At least 235 records · Page 13Linked to original sources
PubMed1983

A gene mapping between the S and D regions of the H-2 complex influences resistance to Trichinella spiralis infections of mice.

The strains B10.S(7R), B10.S(23R) and B10.S(24R), all thought to be genetically identical, differ in levels of susceptibility to infection with Trichinella spiralis. In a series of nine independent experiments, B10.S(7R) was shown to be more susceptible than the other two strains. In another series of seven experiments, the strain B10.A(18R) was shown to be more susceptible to infection with T. spiralis than the strains B10.S(21R) or B10.BAR-5, all of which were thought to share common H-2 alleles. These results indicate that a gene mapping between the S and D loci influences susceptibility to infection with T. spiralis. Typing of these strains for Qa and Tl loci rule out the possibility of a double crossover accounting for the differences observed. The new gene is designated Ts-2. Previously published data have also been reinterpreted and another gene Ts-1 is shown to be associated with The A beta locus. When the d allele is expressed at the Ts-2 locus, strains of mice expressing s, q, f or b alleles at Ts-1 are rendered more susceptible to infection.

Animals↗
PubMed1983

Immune-response gene-associated antigens (Ia/DR). Structure and function in immunologically related diseases.

Major histocompatibility complex-determined antigens were originally identified as a consequence of their ability to induce rejection of tissue grafts between organisms that are not genetically identical. Currently, much is known about their biochemical nature and intended biological functions. Major histocompatibility complex antigens are found on three types of glycoprotein molecules. One type (class I) is associated with beta 2-microglobulin in the cell-surface membranes of all body tissues and includes H-2K and D molecules in mice and HLA-A, B, and C molecules in humans. These antigens are the major cause of rejection of transplanted organs. The other two types of glycoproteins (class II) are noncovalently linked to each other, are found in the cell-surface membranes of a limited number of cell types, and include H-2-Ia molecules in mice and HLA-DR molecules in humans. They are noted for their ability to elicit graft-versus-host disease. Both class I and class II molecules are, however, important for the immune recognition of pathogens, although the types of responses they modulate are different. Class I molecules are important in the recognition of cell-surface antigens, whereas class II molecules control responsiveness to soluble antigens. Major histcompatibility complex-encoded molecules are also involved in certain autoimmune diseases. As our understanding of major histocompatibility complex-controlled immune responsiveness broadens and hybridoma and gene-cloning technology advances, specific enhancement of desired immune responses and suppression of deleterious ones will most likely become possible.

Animals↗
PubMed1983

Immunogenetics of BCG-induced anergy in mice. Control by Igh- and H-2-linked genes.

We previously reported that BCG-induced anergy in mice (evaluated by delayed hypersensitivity to sheep erythrocytes) is unigenic and influenced by genes linked to the immunoglobulin heavy chain allotype (Igh). Using congenic mice (either H-2k or H-2b), we could not detect H-2-linked control of anergy. The current study re-examines this issue by using both BXD (H-2b or H-2d) and BXH (H-2b or H-2k) recombinant inbred (RI) mice as well as H-2 recombinant mice of different haplotypes. BXD RI (H-2b) mice were more anergic than BXD RI (H-2d) animals. Also, BXD RI (Ighb animals were more anergic than BXD RI (Ighc) mice. By evaluating combinations of H-2 haplotypes and Igh allotypes, we found the most anergic animals to be H-2b, Ighb. BCG-induced anergy then appears to be influenced by genes linked to both the H-2 and Igh complexes. BCG-induced anergy developed in H-2 recombinant mice (C57BL/10 background) that were either H-2b or H-2k, but not in H-2d animals. Experiments in the B10.A mouse suggested that genes within the H-2K through H-2I were influential. A more definitive map is presented of Igh-linked genes influencing anergy, suggesting that these genes are approximately 23 recombination units on the centromeric side of Igh-1 between Igh-Src and Lyb-7.

Animals↗
PubMed1983

A survey of susceptibility to infection with Trichinella spiralis of inbred mouse strains sharing common H-2 alleles but different genetic backgrounds.

Twenty-eight different inbred strains of mice representing five different H-2 haplotypes were compared for degree of susceptibility to a primary infection with Trichinella spiralis. Marked differences in susceptibility, measured by the average number of muscle larvae per host, were seen among strains of mice sharing common H-2 alleles. The genes controlling these differences must therefore map at loci outside the major histocompatibility complex. Strains of mice sharing the H-2k haplotype were generally more susceptible than strains expressing other haplotypes and strains expressing H-2q alleles were most resistant. Strains of mice were ranked in order of decreasing susceptibility. Knowledge of these ranking may be of value to researchers wishing to select strains of mice appropriate for studies on T. spiralis.

Alleles↗
PubMed1982

Intragenic recombination in an E beta gene for a murine Ia antigen.

The recombinant strain D2.GD was originally typed as I-Ad by serological methods. Indeed, the A alpha and A beta chains of the I-A antigens appear to exhibit normal behavior by the criteria of serology and two dimensional gel analysis. However, the E beta chain encoded by the I-A subregion of this strain, one of the two components of the plasma membrane located I-E antigens produced in D2.GD X A.TFR5)F1 animals, has been demonstrated to be the product of an intragenic recombinational event between E beta genes from the d and b haplotypes. Sequence analysis suggests that the amino-terminal portion of the Eg2 beta chain is derived from the d haplotype and, therefore, that the coding strand for this gene is oriented centromeric leads to telomeric (5' to 3' direction). Finally, these data combined with the data of Rose and Cullen (17) allow the ordering of the genes within the I-A subregion as (H-2K), A alpha, A beta, E beta ... (H-2D).

Amino Acid Sequence↗
PubMed1982

Genetic control and intersite influences on the immune response to sperm whale myoglobin.

Determination of the precise antigenic structure of sperm-whale myoglobin (Mb) has enabled us to focus our attention on the molecular and cellular factors that control and regulate the immune responses to the protein antigen. Our studies have shown that the immune responses to sperm-whale Mb are controlled by genes in the I region of the major histocompatibility complex (H-2) of mice. More importantly, the responses to the synthetic antigenic sites are each under separate genetic control. The recognition of the antigenic sites by antibodies is independent of the immunized species and of the time the antisera are obtained after the initial immunization (from nine days up to a year). The same sites are recognized by antisera raised in rabbit, goat, pig, cat, chicken and outbred and inbred mice. The same sites recognized by mouse B-cells are also recognized by mouse T-cells. No meaningful genetic control of antibody affinity was observed. Autoimmune antibody and T-lymphocyte proliferative responses were readily generated by immunizing an animal with self-Mb. With mouse Mb, the autoimmune T-lymphocyte response was under genetic control and mapped with the I-A and the H-2D end of the H-2 gene complex. In other recent studies we have shown, using several Mb variants, that the binding capacity of an antigenic site is fully accounted for by substitutions in the antigenic sites (actual contact residues) and in residues close (within 7.A) to the sites (i.e. environmental residues). The overall response to Mb is regulated by inter-site influences which can either be of a cooperative (help) nature or of a suppressive nature. Finally, genetic control of the responses to individual antigenic sites on a protein is not only determined by the genetic constitution of the host but also by the chemical properties of the individual sites. The H-2 subregions mapping the responses to given antigenic sites can also recognize other sites, which were previously unrecognizable in a homologous protein, if the chemical properties of these sites are suitably altered.

Animals↗
PubMed1982

Biochemical evidence for multiple Ia molecules.

Sequential immunoprecipitation and isoelectric focusing studies using anti-Ia monoclonal antibodies have shown multiple I-A and I-E Ia molecules. These studies suggest that the genes coding for Ia polypeptide chains A alpha, A beta, E beta and E alpha might have undergone further duplication and mutated. This would explain the diversity seen with Ia molecules in their ability to "present" numerous self and non-self antigens for generation of immune response.

Animals↗
PubMed1982

Biochemical evidence for multiple I-E Ia molecules.

Sequential immunoprecipitation and isoelectric focusing analyses with monoclonal I-E-specific antibodies presented in this paper indicate the existence of multiple I-E molecules. In sequential immunoprecipitations with 13-4 (anti-Ia.7) and 17-3-3 (anti-Ia.22) monoclonal antibodies, 17-3-3 only partially cleared I-E molecules immunoprecipitated by 13-4. Similarly, 13-4 monoclonal antibody only partially cleared I-E molecules precipitated by 17-3-3 monoclonal antibody. These results suggested a minimum of three I-E molecules. One I-E molecule expresses both 13-4 and 17-3-3 determinants, a second I-E molecule expresses only 17-3-3 determinants, and a third I-E molecule expresses only 13-4 determinants. Isoelectric focusing analyses of I-E molecules immunoprecipitated by 13-4 and 17-3-3 showed differences in both Ae beta polypeptide chains and E alpha polypeptide chains. The sequential immunoprecipitation and isoelectric focusing analyses presented in this paper can be explained by a model in which there are at least two separate Ae genes being encoded within the I-A subregion and two separate E alpha genes being encoded within the I-E subregion. The 17-3-3 monoclonal antibody would recognize a determinant on only one of two Ae beta polypeptide chains and the 13-4 monoclonal antibody would recognize a determinant on only one of two E alpha polypeptide chains.

Animals↗
PubMed1982

Cell-mediated cytotoxicity to non-MHC alloantigens on mouse epidermal cells. VI. Influence of the MHC on the tissue specificity of cytotoxic T-lymphocyte responses.

Mice of the C3H/He and A non-H-2 backgrounds are disparate from mice of the B10 background for the tissue-restricted, non-H-2 alloantigen of epidermal cells (EC), Epa-1, that is expressed by EC but not by lymphocytes (LC), as well as for a number of other alloantigens of the B10 background that are expressed by both EC and LC, generically referred to as "lymphocyte/epidermal alloantigens" (LEA). In this study, we compared the ability of various H-2 congenic strains on the C3H or A backgrounds to mount cytotoxic T-lymphocyte (CTL) responses to EC from H-2 compatible mice of the B10 background. High responses to Epa-1 were detected only in the H-2a and H-2k haplotypes; H-2b, H-2o1, H-2s, H-2t1, and H-2t2 haplotypes were nonresponders to Epa-1. High responses to LEA were detected in H-2a, H-2b, H-2s, H-2t1, and H-2t2 haplotypes; H-2k and H-2o1 were nonresponsive to LEA. Analysis of the H-2K, I and D region alleles of responders indicates that H-2Kk is essential for anti-Epa CTL responses, whereas Dd, Db or Ks were all permissive for strong anti-LEA responses. The ability to mount a given CTL response was not associated with differences in I-region alleles. These results are discussed in terms of K/D region products serving as Ir-gene products for CTL and in determining the apparent tissue-specificity of CTL.

Animals↗
PubMed1982

Biochemical documentation of allelic variation of the I-E antigens of the d, k, p, r, and u haplotypes.

The extent of allelic variation of the E alpha and E beta polypeptide chains of the I-E antigens from the H-2d, H-2k, H-2p, H-2r, and H-2u haplotypes is described. E alpha and E beta chains were individually labeled with arginine or lysine and compared by tryptic peptide analysis. The results indicate minimum variability among the E alpha polypeptides encoded by the d, k, p, and r haplotypes. However, the Eu alpha chain differed significantly from the other allelic E alpha gene products. On the other hand, the E beta alleles demonstrated substantial variability with the Ed beta being notably less similar to the other alleles than they are to each other. These findings are consistent with a number of observations regarding the serology and functions of the I-E antigens.

Alleles↗
PubMed1982

Tumor and histocompatibility antigen interaction: direct visualization by a double-label bridging technique for immuno-electron microscopy.

The nature of the interaction between the Ib tumor-associated surface antigen (Ib-TASA) and the Dk and Kk (Dk/Kk) regions of the major histocompatibility complex on the surface of line Ib lymphocytes was evaluated by immuno-electron microscopy using a double-label bridging technique. Quantitation of antigenic sites by direct counts showed 44% of the Ib-TASA sites coincident with Dk/Kk antigens. This is greater than the predicted random interaction of two independent cell surface determinants suggesting an associative interaction, i.e. 'altered-self' antigen. The remaining 56% of the Ib-TASA sites were in a non-associative mode. On the basis of data presented here, we postulate that the interaction between 'self'- and 'non-self' antigens is not an 'all or none' phenomenon.

Animals↗
PubMed1982

Immune recognition of serum albumin--XIV. Cross-reactivity by T-lymphocyte proliferation of subdomains 3, 6 and 9 of bovine serum albumin.

Recently, we have shown that, with rabbit antibodies against BSA, the BSA fragments 115-184, 307-285 and 505-582 (essentially corresponding to subdomains 3, 6 and 9 of BSA) exhibit a cross-reaction which increases remarkably with the time antisera are obtained after the initial immunization. In the present report, we have examined whether this cross-reaction at the B-cell level takes place also at the T-cell level. Optimum conditions for T-cell proliferation to BSA and the three fragments were determined in terms of priming dose, challenging dose, time lymph nodes are obtained after immunization and finally duration of culture. Several strains of mice representing independent haplotypes and recombinant strains were examined for their responsiveness to BSA by T-lymphocyte proliferation, performed in the respective preimmune sera of the same mice. This afforded the identification of high- and low-responder strains to BSA. It was determined that the immune response to BSA is controlled by genes in the I-A subregion of the H-2 gene complex with some slight non-H-2 influences. In order to avoid the possibility of genetic exclusion of response to a given antigenic site and to improve the change of total site recognition, two high-responder strains (B10.M and B10.G) were crossed. Antibodies raised in (B10.M X B10.G)F1 mice recognized subdomains 3, 6 and 9 and these were found to be cross-reactive. Specific 125I-labelled antibodies isolated on a given subdomain-adsorbent were bound very well by adsorbents of the other two subdomains. T-cells from the F1 mice that had been primed with subdomain 3 responded to subdomain 3 and were also high responders to subdomain 6 and intermediate responders to subdomain 9. After priming with subdomain 6, the T-cells responded equally as well to subdomains 3 or 6 and slightly to subdomain 9. Finally, priming with subdomain 9, gave T-cells that responded to subdomain 9 and also gave high responses to subdomains 3 or 6. It was concluded that the cross-reactions originally observed at the B-cell level also take place at the T-cell level.

Animals↗