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

The minor histocompatibility antigen HA-1 is a peptide derived from the HMHA1 (ARHGAP45) protein, specifically presented by the HLA-A*02:01 major histocompatibility complex (UniProt Q92619). HA-1 is characterized by its restricted expression to the hematopoietic system, including dendritic cells, monocytes, B cells, and their malignant counterparts such as leukemic blasts (PubMed: 10589439). This tissue-specific distribution makes it a highly attractive target for immunotherapy in the context of allogeneic hematopoietic stem cell transplantation (allo-HSCT). By targeting HA-1, therapeutic interventions like TCR-engineered T cells or vaccines can promote a graft-versus-leukemia (GVL) effect while minimizing the risk of graft-versus-host disease (GVHD) in non-hematopoietic organs (PubMed: 9491715). The antigenicity of HA-1 arises from a single nucleotide polymorphism (SNP) that results in a histidine (H) instead of an arginine (R) at the relevant position, creating a non-self epitope in patients receiving transplants from HA-1-negative donors. Current clinical strategies focus on using HA-1-specific T-cell receptor (TCR) therapy to treat relapsed leukemia after transplantation (ClinicalTrials.gov: NCT03326921).

Other names

HMHA1ARHGAP45Minor histocompatibility protein HA-1mHAg HA-1HLA-A2-restricted HA-1 antigen

T-cell receptor (TCR) mediated recognition of the peptide-MHC complex leading to cytotoxic T-lymphocyte activation and targeted cell lysis.