Minor H antigens: genes and peptides

In this review, we describe the evidence from which the existence of non-MHC histocompatibility (H) antigens was deduced, the clinical setting of bone marrow transplantation in which they are important targets for T cell responses, and the current understanding of their molecular identity. We list the peptide epitopes, their MHC restriction molecules and the genes encoding them, of the human and murine minor H antigens now identified at the molecular level. Identification of the peptide epitopes allows T cell responses to these antigens following transplantation of MHC-matched, minor H-mismatched tissues to be enumerated using tetramers and elispot assays. This will facilitate analysis of correlations with HVG, GVH and GVL reactions in vivo. The potential to use minor H peptides to modulate in vivo responses to minor H antigens is discussed. Factors controlling immunodominance of T cell responses to one or a few of many potential minor H antigens remain to be elucidated but are important for making predictions of in vivo HVG, GVH and GVL responses and tailoring therapy after HLA-matched BMT and DLI.