The immunogenomics of minor histocompatibility antigens

Abstract

Minor histocompatibility (H) antigens are a diverse assemblage of major histocompatibility complex (MHC)-bound peptides with the unifying property of acting as alloantigens that induce allogeneic tissue rejection. They are a consequence of any form of accumulated genetic variation that translates to differential MHC-presented peptide epitopes, the most common form of which is simple sequence polymorphisms. The universe of potential minor H antigens is large when transplantation is performed between genetically unrelated, MHC-matched individuals, especially considering the remarkable discriminative sensitivity of T cells. However, the phenomenon of immunodominance greatly simplifies immune responses that ensue. One mouse minor H antigen, H60, stands out in that the preponderance of the CD8 T cell response elicited in a complex alloantigenic setting is directed against this single minor H antigen epitope. Its immunodominance is because mice lacking H60 develop an unusually robust T cell repertoire dedicated to this single minor H antigen. The now well-characterized mouse minor H antigen system should provide a vehicle to assess the degree to which immunodominant alloantigens contribute to transplant rejection.