IDENTIFICATION OF A MOUSE MALE-SPECIFIC TRANSPLANTATION ANTIGEN, H-Y

THE male-specific transplantation antigen, H-Y, causes rejection of ma le tissue grafts by genotypically identical female mice(1) and contrib utes to the rejection of human leukocyte antigen-matched male organ gr afts by human females(2). Although first recognized 40 years ago(1), t he identity of H-Y has remained elusive. T cells detect several distin ct H-Y epitopes(3-5), and these are probably peptides, derived from in tracellular proteins, that are presented at the cell surface with majo r histocompatibility complex (MHC) molecules(6). In the mouse, the gen e(s) controlling H-Y expression (Hya) are located on the short arm of the Y chromosome(7,8) between the zinc-finger genes Zfy-1 and Zfy-2 (r ef. 9). We have recently identified Smcy, a ubiquitously expressed gen e, in this region(10) and its X-chromosome homologue, Smcx(11). Here w e report that Smcy encodes an H-YKk epitope that is defined by the oct amer peptide TENSGKDI: no similar peptide is found in Smcx. These find ings provide a genetic basis for the antigenic difference between male s and females that contributes towards a tissue transplant rejection r esponse.