WHY DO SOME FEMALES REJECT MALES - THE MOLECULAR-BASIS FOR MALE-SPECIFIC GRAFT-REJECTION

The male-specific minor histocompatibility antigen H-Y plays an import ant role in both graft rejection and graft-versus-host disease followi ng transplantation of male tissue into females that are completely mat ched at the major histocompatibility loci. The recent identification o f two peptides that, in association with the mouse H-2K(k) or human HL A B7 major histocompatibility class I molecules, are recognised by H-Y -specific T cells, has provided evidence for the molecular basis for s uch anti-H-Y responses. These peptides are encoded by the mouse and hu man homologues of a ubiquitously expressed Y chromosome gene, Smcy, wh ilst the equivalent peptides encoded by the X chromosome homologues of this gene fail to be recognised. Genetic studies have demonstrated th at, as is the case for other minor histocompatibility antigens, peptid e epitopes from several closely linked genes may be required to intera ct in order to elicit a response against H-Y. Definition of the peptid es and the genes that encode these epitopes will allow the devopment o f tolerogenic protocols that could specifically down-modulate the resp onse to H-Y and perhaps even other minor histocompatibility antigens.