Review lecture. Immunology of H-Y antigen and its role in sex determination.

H-Y was originally discovered as a transplantation antigen that caused female mice of certain inbred strains to reject skin from otherwise identical males. The ability to make the skin graft rejection response and, in vitro, cytotoxic T cell responses against H-Y is controlled by genes within the major histocompatibility complex, H-2, and by non-H-2 genes. H-Y belongs to a class of weak transplantation antigens characterized by an inability to elicit responses under many conditions. Although genetic factors are very important in determining responsiveness, their action can be modified by immunization procedures. H-Y has been proposed as the differentiation signal that causes the formation of the testes from the undifferentiated gonad in the developing embryo. This hypothesis has been explored by using a series of mice whose karyotype and phenotypic sex are paradoxical.