Minor histocompatibility antigen HA-1H presented by HLA-A*02:01 (HA-1H/HLA-A*02:01)

The HA-1H peptide presented by HLA-A*02:01 is a prominent minor histocompatibility antigen (mHAg) derived from the HMHA1 gene, also known as ARHGAP45. This antigen arises from a non-synonymous single nucleotide polymorphism (SNP) that results in a histidine (H) instead of an arginine (R) at a critical position within the peptide sequence VLHDDLLEA, making it immunogenic in HLA-A*02:01-positive individuals. HA-1 expression is highly restricted to the hematopoietic system, including dendritic cells, B cells, monocytes, and their malignant counterparts such as leukemic blasts. This restricted expression profile makes the HA-1H/HLA-A*02:01 complex an ideal target for immunotherapy in the context of allogeneic hematopoietic stem cell transplantation (allo-HSCT). By targeting this complex, clinicians aim to induce a potent graft-versus-leukemia (GVL) effect while minimizing the risk of systemic graft-versus-host disease (GVHD) in non-hematopoietic tissues. Current therapeutic approaches include the development of TCR-engineered T cells and peptide-based vaccines designed to eliminate residual leukemic cells in patients who are HA-1H positive and receive a transplant from an HA-1R homozygous donor.

Other names

HMHA1ARHGAP45Minor histocompatibility protein HA-1HA-1H peptideHLA-A*02:01-restricted HA-1 antigenVLHDDLLEA peptide

Recognition of the HA-1H peptide/HLA-A*02:01 complex by specific T-cell receptors (TCRs) on cytotoxic T lymphocytes (CTLs) leads to the targeted lysis of HA-1-expressing hematopoietic cells, including leukemic blasts.