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Biomedical subjects

D C Shreffler

Publications and source records attributed to D C Shreffler.

At least 109 records · Page 6Linked to original sources
PubMed1973

New lymphocyte antigen system (Lna) controlled by the Ir region of the mouse H-2 complex.

A new system of lymphocyte alloantigens in mice is described. This Lna (lymph-node antigen) system is associated with the Ir region of the H-2 (histocompatibility-2) gene complex. It has the following distinctive characteristics: (1) The gene or genes controlling these antigens has been mapped in the Ir (immune response) region between H-2K and Ss-Slp. (2) The antigens are most readily detectable on lymph-node cells, although they are also expressed on peripheral blood lymphocytes, splenic lymphocytes, and thymocytes. (3) Cytotoxicity against only about half of lymph-node cells is consistently observed. (4) Cytotoxic antibody titers against these antigens are strikingly high-more than 2000 by (51)Cr-release and up to 100,000 in the microcytotoxic test. (5) At least two, probably allelic, forms of the antigen(s) have been defined, one associated with the H-2(k) haplotype and one with the H-2(a) haplotype. (6) Antisera against Lna contain multiple antibody specificities that can be fractionated by absorption either with certain recombinants or with other H-2 halotypes that have crossreactive antigens. The antisera against Lna may be of value for definition and characterization of the products of the Ir and MLR (mixed lymphocyte reaction stimulatory) genes associated with the H-2 complex.

Age Factors↗
PubMed1972

Genetic control of the immune response. Mapping of the Ir-1 locus.

Eleven strains of mice bearing recombinant H-2 chromosomes derived from known crossover events between known H-2 types were immunized with a series of branched, multichain, synthetic polypeptide antigens [(T,G)-A--L, (H,G)-A--L, and (Phe,G)-A--L]. Results with nine of the eleven H-2 recombinants indicated that the gene(s) controlling immune response to these synthetic polypeptides (Ir-1) is on the centromeric or H-2K part of the recombinant H-2 chromosome. Results with two of the eleven recombinant H-2 chromosomes indicated that Ir-1 was on the telomeric or H-2D part of the recombinant H-2 chromosome. Both of these recombinants were derived from crossovers between the H-2K locus and the Ss-Slp locus near the center of the H-2 region. One of these recombinants, H-2(y), was derived from a known single crossover event. These results indicate that Ir-1 lies near the center of the H-2 region between the H-2K locus and the Ss-Slp locus. The results of a four-point linkage test were consistent with these results. In 484 offspring of a cross designed to detect recombinants between H-2 and Ir-1, only two putative recombinants were detected. Both of these recombinants were confirmed by progeny testing. Extensive analysis of one of them has shown that the crossover event occurred within the H-2 region. (Testing of the second recombinant is currently under way.) Thus, in the linkage test, recombinants between H-2 and Ir-1 are in fact intra-H-2 crossovers. These results permit assignment of Ir-1 to a position between the H-2K locus and the Ss-Slp locus.

Animals↗
PubMed1972

Evidence supporting a two-gene model for the H-2 histocompatibility system of the mouse.

The genetic structure of the H-2 system has been traditionally interpreted as consisting of multiple regions controlling histocompatibility antigens. Recently however, many difficulties have been encountered in attempts to construct a single, consistent linear H-2 map on this basis. We have shown that the genetic, serological, and biochemical findings on the H-2 system can be more readily explained by the assumption that there are only two histocompatibility regions (loci) in the H-2 system, H-2D and H-2K, which are separated by loci controlling serum proteins (Ss-Slp), immune response (Ir-1), and perhaps others. Evidence supporting such an interpretation of the H-2 system was obtained by a transplantation analysis of the 14 well-defined H-2 crossovers. F(1) hybrids between different H-2 crossovers were produced and challenged with skin grafts from third party strains. The donor-recipient relationships in these combinations were such that in at least 10 cases the skin grafts should have been rejected if the multiple-region H-2 map is correct but should survive permanently if the two-region model is correct. In all instances, the skin grafts survived permanently, providing further evidence for the two-region map of the H-2 complex.

Animals↗