Minor histocompatibility antigen (MiHA (also written as mHAg))

Minor histocompatibility antigens (MiHAs; also written as mHAgs) are short peptides, generally 9–12 amino acids long, derived from polymorphic proteins that are presented on cell surfaces in the context of MHC (HLA) molecules[1][4][5][6]. These antigens can vary between individuals due to single nucleotide polymorphisms (SNPs), gene deletions, insertions, loss-of-function mutations, and allelic differences on sex chromosomes, especially the Y chromosome[1][2][6]. When allogeneic transplantation (of tissues or hematopoietic stem cells) occurs between HLA-matched individuals, donor T cells and (to a lesser extent) B cells may still recognize recipient-specific MiHAs as foreign, triggering immune responses that mediate graft-versus-host disease (GVHD), graft rejection, or graft-versus-leukemia (GVL) effects. Some MiHAs are ubiquitously expressed, while others have restricted expression, for example, to hematopoietic cells[1][5][6]. Most therapeutically relevant forms involve T cell recognition, and the identification and targeting of hematopoietic-restricted MiHAs is an area of active research for cancer immunotherapy post-transplantation, aiming to exploit the beneficial GVL while minimizing the harmful GVHD[3][4][5]. No classical drugs target MiHAs directly, but adoptive transfer of MiHA-specific T cells and genomic screening for MiHA mismatches are being explored as therapeutic strategies[5][3]. Safety concerns include the risk of off-target tissue injury and the unpredictable nature of immune response due to population genetic diversity[1][3].

Other names

MiHAmHAgMinor-H antigenminor H antigenminor transplantation antigen

Immune recognition (primarily T cell mediated): MiHA peptides are presented on the cell surface by MHC (HLA) molecules; when recognized as non-self by T cells, they provoke cytotoxic or helper T cell responses capable of causing rejection or a graft-versus-leukemia effect[1][4][5]. Antibody responses: Certain MiHAs can also elicit alloantibody production, particularly in settings of solid organ transplantation or prior sensitization[2].