Mechanisms of minor histocompatibility antigen immunogenicity: the role of infinitesimal versus structurally profound polymorphisms.

Minor histocompatibility antigens (mHAgs) are a diverse collection of major histocompatibility complex (MHC)-bound peptides that play a critical role in the induction of detrimental graft-versus-host disease (GVHD) or the development of beneficial graft-versustumor (GVT) effects after allogeneic hematopoietic stem cell transplantation. mHAgs are a consequence of allelic polymorphism that translates to disparity in MHC-presented peptide epitopes between transplant donor and recipient. This donor/recipient allelic disparity can range from infinitesimal amino side chain differences between MHC-presented peptides, to profound structural polymorphisms in genes and proteins that can nullify transcription or translation of one allelic variant and result in the complete abrogation of its presentation by MHC.