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D C Shreffler

Publications and source records attributed to D C Shreffler.

At least 73 records · Page 4Linked to original sources
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↗
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

H-2 restriction of cell-mediated immunity to an intracellular bacterium: effector T cells are specific for Listeria antigen in association with H-21 region-coded self-markers.

The protective activity of anti-Listeria-immune T cells assayed in an adoptive transfer system in H-2 restricted. As shown in the present studies, the demonstration of the restriction is directly dependent on the dose and the relative protective activity of spleen cells. In addition, some H-2-unrestricted protection is conferred predominantly by other than immunoglobulin-negative spleen cells. Thus, the activity of Listeria-immune T cells appears to be 'absolutely' restricted and is in this respect comparable to in vivo T-cell-mediated anti-viral protection. The predominant genetic region of H-2 coding for the structures which are mainly involved in this restriction in T-cell immunity to this prototype intracellular bacterium is the I region. The specificity of Listeria-immune T cells is determined by the H-2 haplotype of the donor. Thus, F1 hybrids seem to possess at least two separable sets of T cells, each specific for one parental haplotype. As is true in the virus model, the results cannot distinguish between an altered-self or a dual recognition model of T-cell recognition to explain H-2 restriction. They are, however, compatible with the idea and I-coded cell surface structures may serve as receptors for cell-specific differentiation signals, which trigger direct or lymphokin-mediated activation of macrophages to manifest increased bactericidal capacity. The interesting parallels in self-marker recognition of T cells in the virus and intracellular bacterium systems, respectively, appear to be reasonably explained by the different types of signals transmitted by T cells to various target cells via the distinctly different self-markers employed (i.e., K or D vs I).

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↗
PubMed1977

Anti-Ia serum blocking of macrophage function in the in vitro humoral response.

Antisera directed at I-region gene products coded for by genes in the I-J subregion effectively block macrophage function in the primary in vitro response to burro erythrocytes. Pretreatment of macrophages with normal serum, nonappropriate anti-Ia antibodies, or anti-H-2 serum had no inhibitory effect. Similar antiserum pretreatment of macrophage-depleted cells did not affect their ability to function with untreated adherent splenic macrophages. The results suggest that the Ia molecule has an active role in antigen presentation by the macrophage or in macrophage-lymphocyte interaction in the primary IgM response.

Animals↗
PubMed1976

Effects of anti-Ia sera on mitogenic responses. III. Mapping the genes controlling the expression of Ia determinants on concanavalin A-reactive cells to the I-J subregion of the H-2 gene complex.

We have shown that the Ia determinants expressed on nylon wool-purified T lymphocytes reactive to concanavalin A (Con A) in serum-free media are coded in a single I subregion of the H-2 gene complex. This region, I-J, is defined by two pairs of intra-H-2 recombinant haplotypes: H-2t3, H-2t4 and H-2i3, H-2i5, carried by B10.HTT, B10.S(9R), B10.A(3R), AND B10.A(5R), respectively. No activity against Con A-reactive T cells has been detected in any antiserum that was produced in strain combinations which shared a common I-J region. This suggests that Ia antigens expressed on Con A-reactive T cells are restricted to the I-J subregion.

Animals↗
PubMed1976

H-2 compatibility requirement for virus-specific T-cell-mediated cytolysis. Evaluation of the role of H-2I region and non-H-2 genes in regulating immune response.

Lymphocytic choriomeningitis virus (LCMV) and ectromelia virus-specific T-cell-mediated cytotoxicity was assayed in various strain combinations using as targets peritoneal macrophages which have been shown to express Ia antigens. Virus-specific cytotoxicity was found only in H-2K- or D-region compatible combinations. I-region compatibility was not necessary nor alone sufficient for lysis. Six different I-region specificities had no obvious effect on the capacity to generate in vivo specific cytotoxicity (expressed in vitro) associated with Dd. Low LCMV-specific cytotoxic activity generated in DBA/2 mice was caused by the non-H-2 genetic background. This trait was inversely related to the infectious virus dose and recessive. Non-H-2 genes, possibly involved in controlling initial spread and multiplication of virus, seem to be, at least in the examples tested, more important in determining virus-specific cytotoxic T-cell activity in spleens than are Ir genes coded in H-2.

Animals↗
PubMed1976

Effects of anti-Ia sera on mitogenic responses. II. Differential expression of the Ia marker on phytohemagglutinin and concanavalin A-reactive T cells.

Genes mapping in the I region of the H-2 complex control a system of lymphocyte alloantigens (Ia) which are expressed on a subpopulation of T cells and on most B cells. Specific anti-Ia serum in the presence of rabbit complement removed the splenic T-cell subpopulation responsive to Con-A, but did not affect the response to phytohemagglutinin (PHA) or Leucoagglutinin. Antibodies specific for Ia, H-2K, or H-2D membrane antigens were used without complement to pretreat spleen cells. These antibody pretreated cells responded normally to Con-A and PHA.

Animals↗
PubMed1976

Separation of anti-Ia (I-region associated antigens) from anti-H-2 antibodies in complex sera, by absorption on blood platelets. description of three new Ia specificities.

H-2 antigens are expressed in substantial amounts of murine blood platelets (for H-2 antigenic content 1 lymphocyte approximately 50 platelets) whereas Ia antigens are probably not expressed at all (minimal Ia antigenic content more than 35 times lower than for H-2). This property of blood platelets makes them very useful for the selective absorption of anti-H-2 antibodies from complex sera and for the preparation of specific anti-Ia antibodies from such sera. In 20 sera produced against the complete H-2 complex, 12 sera contained anti-Ia antibodies beside the expected anti-H-2 antibodies. In two sera, separation of the anti-Ia antibodies was easily obtained by absorption of the anti-H--2 antibodies on platelets. The analysis of one serum (C3H.Q X B10.D2) anti-C3H [(q X d) anti-k] showed that, in addition to be expected anti-H--2.23 and anti-Ia.2 antibodies, it contained at least three other Ia antibodies, separable by absorption on lymphocytes, which recognized three antigens--Ia.17, determined by the haplotypes k, f, s, r, j; Ia.18, determined by the haplotypes k, f, s; and Ia.19 determined by the haplotypes k and r. The genes are located in the I--A and/or I--B subregions of the H--2 complex.

Absorption↗
PubMed1976

Blocking of MLC stimulation by anti-Ia sera: studies with the virus plaque assay.

The development of congenic mouse strains identical at the H-2K and H-2D loci but differing by I-region associated (Ia) determinants has permitted an association to be established between Ia determinants and stimulation in mixed lymphocyte culture reactions (MLR). The present experiments were undertaken to establish whether the Ir-coded control of MLR operated at the level of recognition or of stimulation. Reciprocal MLR were established between A.TH and A.TL mouse spleen cells in the presence or absence of anti-Ia sera directed either at determinants of the stimulating or responding cells. The number of T cells responding was assessed by the virus plaque assay. Anti-Ia sera directed against the responding cells were no more inhibitory of the MLR than normal mouse serum. In contrast, anti-Ia sera directed against determinants of the mitomycin-treated stimulating cells markedly inhibited activation of T cells in the MLR.

Animals↗