Minor histocompatibility antigen HA-1H peptide 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) complex used as a target in immunotherapy for hematologic malignancies. The peptide, typically the nonamer VLHDDLLEA, is derived from the ARHGAP45 protein (also known as HMHA1) and is presented on the cell surface by the HLA-A*02:01 MHC class I molecule (PMID: 9491721). This complex is particularly significant in the context of allogeneic hematopoietic stem cell transplantation (HSCT), where it can mediate a targeted graft-versus-leukemia (GvL) effect (PMID: 10627459). Because ARHGAP45 expression is largely restricted to hematopoietic lineage cells, targeting this complex minimizes the risk of broad graft-versus-host disease (GvHD) in non-hematopoietic tissues (PMID: 11133745). Therapeutic approaches include the development of T-cell receptor (TCR) engineered T cells, such as MDG1021, and peptide-based vaccines designed to specifically recognize and eliminate HA-1H-positive tumor cells (NCT03326921). Clinical development has focused on treating relapsed leukemia and multiple myeloma following stem cell transplants where a mismatch in the HA-1 allele exists between donor and recipient.

Other names

HA-1H/HLA-A2 complexHMHA1 peptide/HLA-A*02:01ARHGAP45 peptide/HLA-A*02:01Minor histocompatibility antigen HA-1VLHDDLLEA/HLA-A*02:01

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