IDENTIFICATION OF AN IMMUNODOMINANT MOUSE MINOR HISTOCOMPATIBILITY ANTIGEN (MIHA) - T-CELL RESPONSE TO A SINGLE DOMINANT MIHA CAUSES GRAFT-VERSUS-HOST DISEASE

T cell responses to non-MHC antigens are targeted to a restricted numb er of immunodominant minor histocompatibility antigens whose identity remains elusive, Here we report isolation and sequencing of a novel im munodominant minor histocompatibility antigen presented by H-2D(b) on the surface of C57BL/6 mouse cells. This nonapeptide (AAPDNRETF) shows strong biologic activity in cytotoxic T lymphocyte sensitization assa ys at concentrations as low as 10 pM, C3H.SW mice primed with AAPDNRET F in incomplete Freund's adjuvant generated a potent anti-C57BL/6 T ce ll-mediated cytotoxic activity, and T lymphocytes from AAPDNRETF-prime d mice caused graft-versus-host disease when transplanted in irradiate d C57BL/6 recipients. These results (a) provide molecular characteriza tion of a mouse dominant minor histocompatibility antigen, (b) identif y this peptide as a potential target of graft-versus-host disease and, (c) more importantly, demonstrate that a single dominant minor antige n can cause graft-versus-host disease, These findings open new avenues for the prevention of graft-versus-host disease and should further ou r understanding of the mechanisms of immunodominance in T cell respons es to minor histocompatibility antigens.