Human Leukocyte Antigen A*02:01-Minor Histocompatibility Antigen HA-1 peptide complex (HLA-A*02:01-HA-1)

The HLA-A*02:01-HA-1 peptide complex is a specific molecular target consisting of the Human Leukocyte Antigen (MHC Class I) allele A*02:01 presenting a peptide derived from the minor histocompatibility antigen HA-1, which is encoded by the ARHGAP45 (formerly HMHA1) gene (UniProt Q92619). HA-1 is a well-characterized minor histocompatibility antigen (mHAg) that is exclusively expressed in the hematopoietic system, including leukemic cells, but is absent in non-hematopoietic tissues (Goulmy et al., 1996, Science). This restricted expression pattern makes the complex a highly attractive target for immunotherapy, particularly in the context of allogeneic hematopoietic stem cell transplantation (ASCT). By targeting this complex, clinicians aim to induce a potent graft-versus-leukemia (GvL) effect to eliminate residual cancer cells while minimizing the risk of systemic graft-versus-host disease (GvHD) in other organs (Spierings et al., 2004, Tissue Antigens). Therapeutic strategies under development include TCR-engineered T cells (TCR-T) and peptide-based vaccines designed to recognize the specific nonamer peptide (VLHDDLLEA) presented by HLA-A*02:01. Current research focuses on optimizing TCR affinity and ensuring the safety of these therapies in patients with hematological malignancies such as acute myeloid leukemia (AML) and multiple myeloma.

Other names

HLA-A*02:01-ARHGAP45 peptide complexMHC-HA-1 complexHLA-A2-HA-1Minor histocompatibility antigen HA-1VLHDDLLEA-HLA-A*02:01 complex

Recognition of the specific VLHDDLLEA peptide presented by the HLA-A*02:01 molecule by engineered or endogenous T-cell receptors (TCRs), triggering cytotoxic T-lymphocyte (CTL) mediated lysis of the target cell.