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J Klein

Publications and source records attributed to J Klein.

At least 955 records · Page 53Linked to original sources

Serologically defined and lymphocyte-defined components of the major histocompatibility complex in the mouse.

The mixed leukocyte culture (MLC) test is an in vitro model of the recognition phase of the homograft response. For the most part, activation in MLC is dependent on differences of the major histocompatibility complex (MHC). Our present studies in the mouse suggest that activation is primarily associated with differences of genetic regions of the MHC other than those which control the serologically defined (H-2) antigens. These differences do not lead to cytotoxic or agglutinating antibody formation despite extensive immunization; we have called these differences lymphocyte-defined (LD) differences. The strongest stimulation in MLC is associated with differences of the Ir region. It is possible that the Ir product is the T cell receptor and that it is this same molecule which can act as the stimulatory agent in MLC. Other possibilities are discussed.

Animals↗

Genetic and immunological complexity of major histocompatibility regions.

There are genetic differences within the major histocompatibility complex of the mouse which lead to skin graft rejection but which cannot be detected serologically. When confronted with these differences on allogeneic cells, lymphocytes proliferate in vitro. In other cases, in vitro lymphocyte proliferation but no skin graft rejection is associated with loci that are linked to but genetically separable from the loci controlling the serologically defined antigens.

Alleles↗

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↗

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↗

Cytological identification of the chromosome carrying the IXth linkage group (including H-2) in the house mouse.

Mus poschiavinus x M. musculus hybrids, which had seven metacentric chromosomes derived from the poschiavinus complement, were repeatedly backcrossed to M. musculus and selected for the chromosome carrying the H-2 complex. A line called T1/Klj was established which had one metacentric chromosome. It was shown by linkage tests and by cytogenetic studies that one arm of this metacentric chromosome corresponds to the M. musculus acrocentric chromosome carrying linkage group IX, in which the H-2 complex is found. The distance from the H-2 locus to the centromere was tentatively estimated as 14 map units.

Animals↗