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Biomedical subjects

C S David

Publications and source records attributed to C S David.

At least 289 records · Page 16Linked to original sources
PubMed1980

Hybrid Ia antigens: genetic, serologic, and biochemical analyses.

Ia specificities 22 and 23 were found to be determinants on hybrid Ia molecules, formed by the noncovalent binding of a 26,000--28,000 dalton beta polypeptide chain (Ae) coded by the I-A subregion and a 32,000--35,000 dalton alpha chain (E alpha) coded by the I-E subregion. For expression of Ia.23 the Ae chain, coded by the I-A subregion, must be derived from the H-2d haplotype, while Ab, As, or Ak can provide the complementing beta chain for the expression of Ia.22. For expression of Ia.22 and Ia.23, most Ia.7 positive strains can provide the complementing alpha chain (E alpha), with the one exception of B10.PL (Eu), which is Ia.7 positive but will not complement with Ad to express Ia.23. Antisera were also produced against hybrid Ia antigens by immunizing with F1 cells expressing Ia.22 or Ia.23 generated by generated by trans-complementation. These antisera detect the same specificities as conventional anti-Ia.22 and anti-Ia.23 sera produced against cis-complementing Ia antigens. It is postulated that hybrid Ia determinants are involved in recognition and generation of immune response to antigens under dual Ir gene control. It is also suggested that there are 2 types of Ia specificities: 1) allotypic Ia specificities expressed on the alpha or beta chains (for example, Ia.7 on the E alpha chain) and 2) hybrid Ia specificities, which are unique interaction determinants formed by the association of alpha and beta chains (for example, Ia.22 and Ia.23). These interaction gene products may be involved in antigen recognition and presentation.

Alleles↗
PubMed1980

Intra-H-2 recombination in the mouse. III. I-Region characterization of haplotypes H-2at2, H-2at3 and H-2a2.

Serological characterization of three K-S interval recombinant strains, TBR2 (H-2at2), TBR3 (H-2at3) and AIR 1 (H-2a2) was performed using anti-H-2, Ia, Ss and Slp antisera. The data presented here reveal that the crossover events in both TBR2 and TBR3 occurred between the I-A and I-E subregions. In both cases, the H-2K and I-A subregions were derived fron the H-2t1 of chromosome, while the I-E, S and H-2D regions were derived from the H-2b chromosome (KsAkEbSbDb). The H-2a2 chromosome resulted from a crossover event between the H-2a1 and H-2i9 chromosomes. Ia and Ss typing of AIR 1 suggested that the K to I-E regions originated from H-2a1 and the S and D regions originated from H-2i9 (KkAkEkSbDd).

Animals↗
PubMed1980

Identity of molecules bearing murine Ia alloantigenic specificities Ia.7 and Ia.22: evidence for a single type of I-E molecule in homozygotes.

In homozygous mice bearing I regions derived from haplotype k, only a single type of Ia molecule bearing the alloantigenic specificities Ia.7 and Ia.22 was found using techniques of sequential immune precipitation and tryptic peptide analysis. As suggested at the fourth Ir Gene Workshop (Sachs 1978), Ia.7 is considered here to be an antigenic determinant associated with I-E-subregion-encoded molecules, i.e., it is excluded from the I-C subregion. The I-C subregion is currently defined mainly by functional traits. It is now known that the I-E molecules are composed of an alpha chain encoded in the I-E subregion, and a beta chain encoded in the I-A subregion. Since the I-C subregion is not involved with the determination of these Ia molecules, and since in homozygotes there is apparently only a single type of molecule bearing both specificities Ia.7 and Ia.22, the term "I-E/C" molecule should probably be dropped in favor of the simpler designation I-E.

Animals↗
PubMed1980

Gene complementations to generate Ia antigens (Ia.23) on hybrid molecules.

Ia specificity 23 is a "combinatorial" antigen generated on a hybrid I region molecule, formed by the noncovalent binding of a 26,000- to 28,000-dalton beta polypeptide chain (Ae) coded by a gene in the I-A subregion with a 32,000- to 35,000-dalton alpha chain (E alpha) coded by a gene in the I-E subregion of the mouse H-2 gene complex. For expression of Ia.23, the Ae chain must be derived from the H-2d haplotype (I-Ad), while the E alpha can be provided by I-Ed, I-Ek, I-Ep, I-Er, I-Ev, and I-Ew3, but not I-Eb, I-Ef, I-Eq, I-Es, and I-Eu. With the exception of H-2u haplotype, all Ia.7 (I-E)-positive haplotypes can provide the permissive E alpha chain for generating Ia.23 by trans-complementation. In the H-2d haplotype, Ia.23 is generated by cis-complementation of Ad with Ed. Lymphocytes of F1 animals expressed two I-E subregion coded hybrid Ia specificities; one formed by cis-complementation and another by trans-complementation. It is postulated that such hybrid determinants are involved in the recognition and generation of immune response to antigens such as GL-Phe and cytochrome C where dual Ir gene control has been demonstrated. It is also suggested that there are two types of Ia specificities: (1) allotypic Ia specificities expressed on the alpha or beta chains (these could aid in the binding between the alpha and beta chains such as Ia.7); and (2) hybrid Ia specificities which are unique interaction determinants formed by the specific association of the alpha and beta chains (e.g., Ia.22,23). These interaction gene products may be involved in antigen recognition and presentation.

Animals↗
PubMed1980

Antigen-pulsed neutrophils bearing Ia antigens can induce T lymphocyte proliferative response to the syngeneic or semisyngeneic antigen-primed T lymphocytes.

Antigen-pulsed neutrophils from mouse peritoneal cavities displayed a remarkable level of lymphocyte proliferative activities to antigen-primed T lymphocytes. Genetic mapping studies demonstrated that compatibility at the I-A, as well as I-E/C, subregions of the major histocompatibility complex (MHC) was essential for effective presentation of the lysozyme antigen. These antigen-presenting activities were remarkably inhibited by anti-Ia sera. Inhibition tests revealed that neutrophil immune-associated (Ia) antigens seem to be essential for antigen presentation during the initial 8 hr. Elimination studies of antigen-pulsed neutrophils with alloantisera plus complement revealed these antigen-presenting neutrophils bearing both I-A and I-E/C gene products on the same cells. These results suggest that Ia-positive neutrophils might play a role in the immune response through antigen presentation.

Animals↗
PubMed1980

Lack of gene complementation prevents expression of I-Ek in recombinant A.TFR5.

The I-E molecule is produced by complementation of genes in I-A (Ae) and I-E (E alpha). Ia specificities 22 and 23 are generated by the hybrid molecule, whereas Ia.7 is an allotypic determinant presumably on the alpha-chain of the I-E molecule. Recombinant A.TFR5 (AfEk) lacks detectable I-E molecule since Af and Ek cannot complement. In a cross between A.TFR5 and B10.A(4R) (AkEb), Aek and E alpha k can successfully complement to express the I-Ek molecule on the cell surface of the heterozygote. Haplotypes H-2b and H-2s can also provide the permissive Abe and Ase molecules for complementation with Ek alpha of A.TFR5.

Absorption↗
PubMed1979

Regulatory mechanisms in cell-mediated immune responses. VIII. Differential expression of I-region determinants by suppressor cells and their targets in suppression of mixed leukocyte reactions.

The phenotypic expression of I-region determinants on cells producing and responding to MLR suppressor factor (MLR-TsF) was established in these studies. Alloantigen-activated MLR suppressor T cells (MLR-Ts), which produce MLR-TsF bearing gene products of the I-C subregion, were exposed to anti-I subregion sera and complement (C) before in vitro culture for MLR-TsF production. Suppressor activity was prevented by removal of cells bearing I-C determinants, whereas elimination of cells expressing I-A/B determinants had no effect. Interestingly, cytotoxic elimination of cells displaying I-J determinants also prevented MLR-TsF production. Admixture of anti-I-J and I-C antiserum-treated cells for MLR-TsF production failed to reconstitute suppressor activity, indicating that I-C and I-J gene products are expressed on a single population of cells critical to MLR suppression, rather than on distinct interacting subpopulations. Anti-I-C serum activity specific for I-C+ MLR-Ts was removed by adsorption with nylon wool-nonadherent splenic T cells and concanavalin A-activated thymocytes; adsorption with splenic B cells from anti-Thy-1,2 serum and C-treated spleen failed to remove relevant anti-I-C activity. These data suggest that regulatory I-C molecules, like I-J molecules, are preferentially expressed on T lymphocytes. Expression of I-C, or other I-region molecules on responder cell targets of MLR-TsF activity was also investigated. Responder cells were pretreated with anti-I subregion-specific sera in blocking or complement-dependent cytotoxic protocols before addition to MLR with MLR-TsF. Neither blocking nor the cytotoxic removal of cells bearing I-C or other I-region determinants from MLR responder populations interfered with MLR-TsF suppression. Because it has previously been demonstrated that MLR-TsF interacts optimally with activated, I-C syngeneic target cells, blocking and cytotoxic studies with anti-I subregion sera were also performed with responder cells activated by 24 h culture in MLR in the absence of MLR-TsF. Brief MLR-TsF pulse after antiserum treatment generated marked suppression regardless of blocking or absence of cells bearing serologically detected I-region determinants. I-C restricted suppression may thus be mediated not by interaction with I-C-bearing cells, but by target cells which exist in requisite association with populations of I-C+ cells.

Animals↗
PubMed1979

Regulatory mechanisms in cell-mediated immune responses. VII. Presence of I-C subregion determinants on mixed leukocyte reaction suppressor factor.

The presence of H-2 gene products on mixed leukocyte reaction (MLR) supressor factor was investigated by passage of MLR-suppressor factor (SF) over solid immunoadsorbents prepared with various anti-H-2 subregion sera. Antisera with specificity for all or certain I subregion determinants removed or significantly reduced suppressor activity; adsorption was not consistent with K or D region specificity. The single I subregion specificity common to all adsorbing preparations was I-C. Serologic differentiation of I-C products of k and d haplotypes expressed on MLR-SF was established with antisera prepared in I-Cd/I-Ck disparate strain combinations. These sera define allelic T cell restricted Lad determinants encoded by I-C genes. MLR-SF prepared from (BALB/c X CBA)F1 mice and exposed to the I-Cd and I-Ck specific adsorbents demonstrated d and k haplotype specific adsorption respectively. F1 suppressor activity adsorbed on an anti-I-Cd column was eluted by glycine-HCl buffer and suppressed only BALB/c (H-2d) responses. B10.A suppressor activity was removed by anti-I-Cd sera, but was unaffected by anti-I-Ck sera, indicating that B10.A suppressor activity is encoded by an I-C subregion derived from the d haplotype. Antisera with anti-I-Jk specificity did not remove suppressor activity of various H-2k factors. Finally, adsorption with antisera directed against H-2-associated determinants of the allogeneic cell used to stimulate suppressor factor generation demonstrated that sensitizing alloantigens are not components of MLR suppressor factor. Thus among the major histocompatibility complex (MHC)-controlled suppressor factors, MLR suppressor factor is uniquely determined by the I-C subregion.

Animals↗
PubMed1979

Serological analysis of antigen-specific helper factors specific for poly-L(Tyr, Glu)-poly-DLAla--poly-LLys [(T, G)-A--L] and L Glu60-LAla30-LTyr10 (GAT).

In vitro prepared antigen-specific helper factors reactive to the synthetic polypeptide antigens poly-L(Tyr, Glu)-poly-DLAla--poly-LLys [(T, G)-A--L] or LGlu60-LAla30-LTyr10 (GAT) and bearing Ia determinants were analyzed serologically to determine the nature of the Ia determinants they expressed. I subregion-specific mouse anti-Ia antisera were used, and showed that (T, G)-A--L-specific helper factor (HF) contains I-A subregion-controlled determinants, whereas GAT-specific HF carries I-J subregion-controlled antigens. This unexptected finding was confirmed in both the H-2k and H-2 b haplotypes, using a variety of anti-I-J antisera. Rabbit anti-Ia antisera also reacted with both HF which raised the possibility that the Ia determinants on HF may be carbohydrate in nature. The fact that HF has a low molecular weight and yet contains Ia determinants, antigen-binding capacity and idiotypic markers is compatible with this interpretation.

Adsorption↗
PubMed1979

Differences in the susceptibility of MHC and non-MHC mixed lymphocyte reactions to suppression by murine amnionic fluid and its components.

The ability of mouse amniotic fluid (MAF), alpha-foetoprotein (AFP) and MAF depleted of AFP (MAF - AFP) to suppress primary one-way MLR's was investigated. It was found that MAF, AFP and MAF - AFP were all suppressive of MLR's specific for MHC, K, D or I + S determinants. Suppression was observed when either lymph node or spleen cells were used as the responder cells. Nylon wool column passage of these cells did not significantly affect the immunosuppressive action of these substances. In contrast, MLR's specific for non-MHC/M-locus determinants demonstrated either diminished suppression or augmentation of the response, compared with the MHC stimulated MLR's. Our results show a differential effect of whole MAF and its fractions on the proliferative responses induced by various allogeneic stimuli and suggest that suppression is not due to a non-specific effect on proliferation regardless of the stimulus or cell type involved.

Amniotic Fluid↗
PubMed1979

Genetic control of the immune response to hen's egg-white lysozyme in mice. I. Antibody and T-lymphocyte proliferative responses to the native protein.

We have initiated studies to determine whether the antibody and T-lymphocyte proliferative responses to lysozyme and its antigenic sites is genetically controlled in mice. Mice of the H-2f, H-2k and H-2p were high responders, while haplotypes H-2b, H-2d, H-2r and H-2s were low responders. Studies with recombinants indicated that the immune response is controlled by two H-2I region loci, one being in the I-A subregion and the other may be in the I-C subregions.

Animals↗
PubMed1979

Regulation of autoimmune response to mouse thyroglobulin: influence of H-2D-end genes.

Studies were initiated to define the H-2-linked genetic control of response to self-determinants of MTg. In addition to the Ir gene control of H-2K end, a modifying effect of D end was seen. The extent of regulation depended upon the derivation of the K-end Ir-Tg gene(s) as well as the D-end genes. When the Ir-Tg gene was from good responder H-2k and H-Ss strains, and the H-2D-end gene from the d allele, antibody levels were moderate to high but cellular infiltration was significantly reduced. These findings demonstrate genetic interaction between I-region and D-end gene products in the response to a self-antigen, MTg.

Alleles↗