Minor histocompatibility antigen HA-1 peptide in complex with HLA-A*02:01 (HA-1/HLA-A*02:01)

The HA-1 peptide in complex with HLA-A*02:01 is a well-characterized minor histocompatibility antigen (mHAg) complex that serves as a significant target in cancer immunotherapy, particularly for hematologic malignancies. The HA-1 peptide (VLHDDLLEA) is derived from the ARHGAP45 (formerly HMHA1) protein, which is predominantly expressed in the hematopoietic system, including leukemic cells (den Haan et al., Science, 1998). When presented by the HLA-A*02:01 MHC class I molecule, this complex can be recognized by specific T-cell receptors (TCRs), triggering a potent cytotoxic immune response (Mutis et al., Blood, 1999). Because its expression is largely restricted to blood cells, it is an ideal target for the graft-versus-leukemia (GvL) effect following allogeneic stem cell transplantation without inducing widespread graft-versus-host disease (GvHD) in non-hematopoietic tissues (Goulmy et al., NEJM, 1996). Therapeutic strategies targeting this complex include TCR-engineered T-cell therapies (TCR-T), peptide-based vaccines, and TCR-like antibodies designed to selectively eliminate HA-1-positive malignant cells (Kirschner et al., 2002; van Loenen et al., 2011). The clinical application of this target is highly dependent on the patient's HLA type and the presence of the HA-1-encoding allele (rs1801284).

Other names

HA-1/HLA-A2 complexmHAg HA-1VLHDDLLEA/HLA-A*02:01HMHA1 peptide/HLA-A*02:01ARHGAP45 peptide/HLA-A*02:01

T-cell receptor (TCR) mediated recognition of the peptide-MHC complex leading to T-cell activation and targeted lysis of HA-1-expressing cells.