Minor histocompatibility antigens: time for a paradigm shift?

Minor histocompatibility antigens (mH-Ags) are polymorphic proteins that are capable of eliciting immune responses between HLA-matched donor and transplant recipient. These immune responses are mediated by T cells that recognize antigenic peptides generated from mH proteins. Although the prerequisite of matching the major histocompatibility complex encoding alleles for successful transplant acceptance is well appreciated, knowledge on the role of mH-Ags in graft rejections and their use in immunotherapeutic applications is far from complete. Therefore, the first objective of this review is to compile comprehensive information regarding murine and human mH-Ags. Secondly, recent studies have revealed that several full-length mH proteins possess novel cellular and immunological functions. Because these specialized functions of mH proteins have the potential to modulate clinical outcomes, this review will attempt to summarize all known functions of mH proteins and discuss a paradigm shift that is currently taking place to redefine the immunobiology of these antigens.