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

The HA-1 peptide presented by HLA-A*02:01 is a well-characterized minor histocompatibility antigen (mHAg) derived from the HMHA1 gene (also known as ARHGAP45). This specific antigen is formed by a non-synonymous single nucleotide polymorphism (SNP) that results in a histidine (H) instead of an arginine (R) at the relevant position of the VLHDDLLEA peptide sequence. Because HA-1 expression is largely restricted to the hematopoietic system, including leukemic cells, it serves as an ideal target for immunotherapy following allogeneic hematopoietic stem cell transplantation (HSCT). In this clinical setting, donor-derived T cells can be engineered or primed to recognize the HA-1/HLA-A*02:01 complex on the patient's residual tumor cells, inducing a potent graft-versus-leukemia (GvL) effect with a reduced risk of systemic graft-versus-host disease (GvHD). Current therapeutic strategies targeting this complex include TCR-engineered T-cell therapies and peptide-based vaccines designed to eradicate hematological malignancies.

Other names

HA-1 antigenHMHA1 peptidemHAg HA-1VLHDDLLEA peptideRho GTPase activating protein 45 (ARHGAP45) peptide

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