Comparative immunogenicity and enhanceability of individual H-2K and H-2D specificities of the murine histocompatibility-2 complex.

The immunogenicity of single, private H-2 specificities has been tested. In most cases, the specificity was known to be confined either to H-2K or to H-2D. This was accomplished by the appropriate choice, as donor and recipient, or parent of the F(1) hybrid recipient, of congenic strains differing at H-2 only, and of recombinant haplotypes in donor and/or recipient. By nearly all tests, the H-2K antigen appeared to be a stronger immunogen than the H-2D antigen. Skin grafts with an H-2K difference showed median survival times (MST) of 9.3-14.5 days; for H-2D the values were 13.8-18.6. The difference was also present, though narrowed, for second-set grafts. H-2K grafts regularly engendered a demonstrable cytotoxic antibody response; with H-2D differences the response was absent or very weak. K end cytotoxic titers after multiple immunizations with lymphoid tissues ranged from 1/32 to 1/2,048, D end titers from 0 to 1/128. Hemagglutination titers showed no clear difference. The results of passive enhancement of skin grafts with H-2 alloantibody produced in donor recipient combinations, identical to those used for the skin grafts showed a different pattern. H-2K, despite its greater immunogenic strength was more easily enhanced than H-2D. Prolongation of MST's for H-2K was 2.4-6.7 days, for H-2D grafts, 0.2-1.5 days.

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.