The human UTY gene encodes a novel HLA-BS-restricted H-Y antigen

The mammalian Y chromosome encodes male-specific minor histocompatibility ( H-Y) Ags that are recognized by female T cells in an MHC-restricted manner. Two human H-Y epitopes presented by HLA-A2 and HLA-B7, respectively, have been identified previously and both are derived from the SMCY gene. We prev iously isolated CD8(+) CTL clones that recognized a male-specific minor his tocompatibility Ag presented by HLA-BS. In contrast to the SMCY encoded H-Y epitopes, the B8/H-Y Ag was not presented by fibroblasts from male donors, suggesting that it was encoded by a novel gene. We now report that the HLA -B8-restricted H-Y epitope is defined by the octameric peptide LPHNHTDL cor responding to aa residues 566-573 of the human UTY protein. Transcription o f the UTY gene is detected in a wide range of human tissues, but presentati on of the UTY-derived H-Y epitope to CTL by cultured human cells shows sign ificant cell-type specificity. Identification of this CTL-defined H-Y epito pe should facilitate analysis of its contribution to graft/host interaction s following sex-mismatched organ and bone marrow transplantation.