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C S David

Publications and source records attributed to C S David.

At least 325 records · Page 18Linked to original sources

Evidence for more than one Ia antigenic specificity on molecules determined by the I-A subregion of the mouse major histocompatibility complex.

Ia antigenic specificities determined by the I-A subregion of the mouse major histocompatibility complex have been examined in strain B10.D2 (H-2d), C57BL/10 (H-2b), and in a (C57BL/6xDBA/2) hybrid (BDF1; H-2b/d). Detergent solubilized, 3H-leucine-labeled antigen preparations were mixed with appropriate alloantisera and precipitation was induced either by addition of goat anti-mouse gamma-globulin or by addition of protein A-bearing Staphylococci. Sequential precipitation analysis showed that in strain B10.D2, Ia specificities 8 and 11 were co-precipitable, and that in strain C57BL/10, Ia specificities 8 and 9 were co-precipitable. In contrast, precipitation of specificities 9 and 11 from a BDF1 antigen preparation showed that these two Ia specificities were on separate molecules. The genetic implications of these data are discussed.

Animals↗

Antigen-specific T-cell factor in cell cooperation. Mapping within the I region of the H-2 complex and ability to cooperate across allogeneic barriers.

Further mapping of the mouse T-cell factor specific for poly(Try,Glu)-polyD-LAla--polyLys is reported. It is shown to be a product of the I-A subregion of the H-2 complex by the use of antisera either raised specifically against or made specific, by absorption, for different regions of the H-2 complex. The factor cooperates across allogeneic barriers, e.g., when factor produced by one strian is combined with bone marrow cells of other H-2 incompatible strains.

Animals↗

Interactions of Fc receptors with antibodies against Ia antigens and other cell surface components.

Two Fc receptor-dependent tests were investigated to study the question of a relationship between Fc receptors and known cell surface antigens, in particular I region-associated (Ia) antigens: (a) a rosette assay with antibody-coated erythrocytes (EA) as indicator cells and normal mouse lymphoid cells as source of rosette-forming cells, and (b) a cytotoxicity test with antibody-coated erythrocytes as target cells and normal mouse spleen cells as a source of cytotoxic cells (K cells). EA rosettes were specifically inhibited by antibodies reacting with Ia antigens. Various other antisera reacting with antigens on B lymphocytes, like anti-Ly 4.2 (raised in H-2 identical mice), rabbit antimouse B-cell serum, or rabbit antimouse immunoglobulin, also specifically inhibited the rosettes. No inhibition occurred in the presence of allogeneic or xenogeneic antisera reacting with T lymphocytes. K-cell cytotoxicity was specifically inhibited by each of the antisera (reacting with either B cells or T cells). F(ab')2 fragments of anti-Ia antibodies could still specifically inhibit EA rosettes but they could not inhibit K-cell cytotoxicity. Similar results were obtained with F(ab')2 fragments of anti-immunoglobulin antibodies. These results indicate that the mechanism of inhibition of Fc receptors in the two tests was different. In neither of the tests could we find any evidence for a unique association between the Fc receptors and Ia antigens. The Fc receptors on K cells did not seem to be associated at all with Ia antigens.

Animals↗

I-region-associated determinants: expression on mitogen-stimulated lymphocytes and detection by cytotoxic T cells.

We have studied the expression of Ia-antigens, controlled by genes in the I-region of the H-2 complex, on phytohemagglutinin (PHA)-stimulated lymph node cells and on lipopolysaccharide (LPS)-stimulated spleen cells, and have compared these two types of cell populations as targets for killer cells in the cell mediated lympholysis (CML) assay. PHA targets are almost completely insensitive to complement-mediated lysis by anti-Ia sera while the majority of LPS targets are killed. T cell-mediated lysis against I-region determinants was also detected, and these determinants, in contrast to H-2K and H-2D CML determinants, seem to be much more strongly expressed on LPS-stimulated cells. No differences in the kinetics of the response to K- or I-region CML determinants were observed. Lysis by killer cells can also be obtained against incompatibilities which do not give rise to strong skin graft rejection and against determinants which are most probably controlled by genes outside the K-D interval.

Animals↗

Studies on recombination within the mouse H-2 gene complex. III. Further serological analyses of the H-2t haplotypes.

The five H-2t haplotypes are all intra-H-2 recombinants which have identical K and D regions, but differ in the central regions of the complex. Analyses of H-2, Ia and Ss-Slp types indicate that the crossover in H-2t1 took place between the K and I regions, in the H-2t2 between G and D, in H-2t3 and H-2t4 between the I-B and I-C subregions and in H-2t5 between I and S. The set of recombinants will be very valuable for studies of traits which map in the I and S regions.

Animals↗

Serologic and biochemical studies of the Ia system of the mouse H-2 gene complex. Further evidence for I-C subregion.

Three antisera were made against B10.A(5R) tissues to show the presence of an I-Cd subregion in that strain: 1) B10 anti-B10.A(5R) [anti-Dd, I-Cd]; 2) (B10 times C3H.9L) F1 anti-B10.A(5R) [anti-Ddi1; 3) (B10 times HTI)F1 anti-B10.A(5R) [anti-I-Cd]. Serologic analyses of the antisera clearly showed the presence of an Id segment in B10.A(5R) and provided further evidence for the existence of a new I-C subregion. These anti-I-Cd sera define the Ia.7 specificity and analyses of several recombinants map Ia.7 within the I-C subregion. Ia.7 is present in I-Ck, I-Cd and Ip strains. Biochemical analyses showed that the Ia.7 molecule has a molecular weight of 31,000 and is distinct from the 46,000 m.w. H2K or D molecules. The possible roles of the I-C region in immune response, mixed lymphocyte reaction, and graft-vs-host reaction are discussed.

Absorption↗

Ir-associated murine alloantigens. Serological and chemical definition of Ia specificities associated with the H-2-b haplotype.

Strains bearing recombinant H-2 haplotypes with known positions of recombination have been used to demonstrate antibodies reacting with Ia antigens associated with the H-2-b haplotype in several H-2 antisera. Two new Ia specificities, Ia.8 and Ia.9, both determined by genes in the Ir-1A subregion, have thus been defined, and the strain distribution of these specificities has been determined. Immunoprecipitation of radio-labeled membrane antigens has been used to characterize Ia.9 and to distinguish it chemically from Ia.7 in a membrane preparation from a strain possessing both specificities.

Animals↗

Evidence for the expression of Ia (H-2-associated) antigens on thymus-derived lymphocytes.

We have demonstrated in an anti-Ia serum the presence of specific antibodies reacting with T cells, as well as with B cells, using a highly sensitive dye exclusion test. This antiserum reacts with both spleen and lymph node in a characteristic biphasic titration curve killing up to 70% of these cells. It also reacts with cortisone-resistant thymocytes. The A.TH-alpha-A.TL serum can be absorbed with spleen, lymph node, cortisone-resistant thymus, or normal thymus cells. Further in vivo absorptions in BALB/c nude cannot remove all of the cytotoxic activity for normal BALB lymph node lymphocytes, while completely removing the activity for nude cells. A Thy-1 positive cell line derived from a C57Br leukemia is reactive with this anti-Ia serum.

Animals↗

The presence of I-region-associated antigens on B cells in molecules distinct from immunoglobulin and H-2K and H-2D.

The distribution of I-region-associated antigenic specificities in murine lymphoid cells was studied by immunofluorescence. The antigens were mostly represented in B cells and in macrophages. The complexes of I-anti-I-region-associated antigens were found to be distributed throughout the lymphocyte surface both at 4 degrees and 37 degrees . In about two-thirds of the lymphocytes the complexes redistributed into caps after incubation with a second ligand (an anti-mouse immunoglobulin). The I-region specificities were in molecules distinct from immunoglobulin or from the molecules coded by the H-2K and H-2D regions.

Animals↗

Membrane molecules determined by the H-2 associated immune response region: isolation and some properties.

Membrane associated molecules that are probably glycoproteins could be specifically precipitated from NP-40 detergent solubilized extracts of radiolabeled mouse spleen or lymph node cells by antisera produced in congenic strain combinations differing only in the Ir gene region which is linked to the H-2 genes. These Ir region products were designated Lna (lymph node antigen) to conform to previous serological work.Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of unreduced specific immune precipitates revealed the presence of a possible dimer form, while reduced samples showed only a single peak equivalent to 30,000 daltons. Thus the Lna molecules are clearly distinct from the H-2D and H-2K molecules, which are about 45,000 daltons. Anti-Lna antibodies of different specificity can be present in a single serum; there were at least two separate antigen molecules present in one haplotype tested.

Animals↗