Minor histocompatibility antigen HA-1 and HA-2 peptide–HLA-A*02:01 complexes (HA-1/HA-2–HLA-A*02:01)

The HA-1 and HA-2 peptide–HLA-A*02:01 complexes are well-characterized minor histocompatibility antigens (mHags) that play a critical role in the immune response following allogeneic hematopoietic stem cell transplantation (HSCT). These complexes consist of specific polymorphic peptides—derived from the HMHA1 (ARHGAP45) and MYO1G genes, respectively—bound to the HLA-A*02:01 molecule. Because these antigens are primarily expressed on hematopoietic cells, including leukemic blasts, they serve as ideal targets for inducing a graft-versus-leukemia (GvL) effect without causing widespread graft-versus-host disease (GvHD) in non-hematopoietic tissues. Therapeutic strategies targeting these complexes include the use of peptide vaccines and T-cell receptor (TCR) engineered T-cells designed to specifically recognize and eliminate malignant cells in HLA-matched, mHag-mismatched transplant settings. The restricted expression pattern of HA-1 and HA-2 makes them highly attractive for precision immunotherapy in patients with hematologic malignancies such as leukemia and multiple myeloma.

Other names

mHag HA-1–HLA-A*02:01 complexmHag HA-2–HLA-A*02:01 complexHuman leukocyte antigen A*02:01–HA-1 peptide complexHuman leukocyte antigen A*02:01–HA-2 peptide complexHMHA1-derived peptide–MHC complexMYO1G-derived peptide–MHC complex

Drugs targeting these complexes, such as TCR-engineered T-cells, recognize the specific peptide-MHC complex on the surface of malignant cells, leading to targeted cytotoxicity and the induction of a graft-versus-leukemia (GvL) effect.