THE MALE-SPECIFIC HISTOCOMPATIBILITY ANTIGEN, H-Y - A HISTORY OF TRANSPLANTATION, IMMUNE-RESPONSE GENES, SEX DETERMINATION AND EXPRESSION CLONING

H-Y was originally discovered as a transplantation antigen. In vivo pr imary skin graft responses to H-Y are controlled by immune response (I r) genes mapping to the MHC. In vitro T cell responses to H-Y are cont rolled by MHC class I and II Ir genes, which-respectively, restrict CD 8 and CD4 T cells: These can be isolated as T cell clones in vitro. T cell receptor (TCR) transgenic mice have been made from the rearranged TCR genes of several of these, of which that specific for H-Y/D-b is the best studied. Non-MHC Ir genes also contribute to the control of i n vitro CTL responses to H-Y. The Hya/HYA gene(s) encoding H-Y antigen have been mapped using translocations, mutations, and deletions to Yq in humans and to the short arm of the Y chromosome in mice, where the y lie in the deletion defined by the Sxr(b) mutation between Zfy-1 and Zfy-2. Hya/HYA has been separated from the testis-determining gene, S ry/SRY, in both humans and mice and in humans the azoospermia factor A ZF has been separated from HYA. In mice transfection of cosmids and cD NAs mapping to the Sxr(b) deletion has identified two genes encoding H -Y peptide epitopes. Two such epitopes, H-Y/K-k and H-Y/D-k, are encod ed within different exons of Smcy, and a third, H-Y/D-b, by a novel ge ne, Uty. Peptide elution approaches have isolated a human H-Y epitope, H-Y/HLA-B7, and identified it as a product of SMCY. Each of the Hya g enes in mice is ubiquitously expressed but of unknown function. Their X chromosome homologues do not undergo X inactivation.