The genetic control of the immune response to H-4 histocompatibility alloantigens is described. The rejection of H-4.2-incompatible skin grafts is regulated by an H-2-linked Ir gene. Fast responsiveness is determined by a dominant allele at the IrH-4.2 locus. The H-2b, H-2d, and H-2s haplotypes share the fast response allele;H-2a has the slow response allele. Through the use of intra-H-2 recombinants, we have mapped the IrH-4.2 locus to the I-B subregion of the H-2 complex; the H-2h4, H-215, and H-2t4 haplotypes are fast responder haplotypes. These observations suggest that the strength of non-H-2 histocompatibility antigens is ultimately determined by the antigen-specific recipient responsiveness.
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