The cytotoxic T cell response to the male-specific histocompatibility antigen (H-Y) is controlled by two dominant immune response genes, one in the MHC, the other in the Tar alpha-locus

The genetic control of the cytotoxic T-cell response to the male histocompatibility antigen, H-Y, was analyzed in BALB/cKe(C) and SJL/J(J) which are both nonresponders. However, the (C X J)F1 hybrid is a responder. Therefore, two dominant complementing genes are involved. Analysis of a set of (C X J) recombinant inbred (RI) lines reveals that these two complementing gene products are a restricting element (R) encoded by the H-2 (MHC) locus on chromosome 17 and a subunit of the T- cell receptor (anti-R) encoded by the Tar alpha-locus on chromosome 14. The order and orientation of gene segments within the Tar alpha-locus has also been established relative to the chromosome 14 marker, Es-10. The existence of two RI strains which are recombinant at chromosome 14 has made it possible to determine that this order is Es-10--v alpha-1-- v alpha-2--[C alpha--Np-2]--centromere. The implications of these data for the antigen-specific regulation of immune responsiveness are discussed in terms of the dual recognitive-single receptor model.