Minor histocompatibility antigens: presentation principles, recognition logic and the potential for a healing hand

Abstract

There is ample evidence indicating a pathologic role for minor histocompatibility antigens in inciting graft-versus-host disease in major histocompatibility complex (MHC)-matched bone marrow transplantation and rejection of solid organ allografts. Here we review the current knowledge of the genetic and biochemical bases for the cause of minor histoincompatibility and the structural basis for the recognition of the resulting alloantigens by the T-cell receptor. Recent evidence indicates that we as independently conceived individuals are genetically unique, thus, offering a mechanism for minor histoincompatibility between MHC-identical donor-recipient pairs. Furthermore, advances in delineating the mechanisms underlying antigen cross-presentation by MHC class I molecules and a critical role for autophagy in presenting cytoplasmic antigens by MHC class II molecules have been made. These new insights coupled with the X-ray crystallographic solution of several peptide/MHC-T-cell receptor structures have revealed mechanisms of histoincompatibility. On the basis of these new insights, ways to test for allograft compatibility and concoction of immunotherapies are discussed.