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

The Minor histocompatibility antigen HA-1 peptide–HLA-A*02:01 complex is a lineage-specific immunological target used in the treatment of hematological malignancies. It consists of a nonameric peptide (VLHDDLLEA) derived from the Rho GTPase-activating protein 45 (ARHGAP45/HMHA1) protein, presented on the cell surface by the Human Leukocyte Antigen allele A*02:01 (Goulmy et al., 1996; UniProt Q92619). Because HMHA1 expression is strictly limited to hematopoietic cells—including hematopoietic stem cells, leukocytes, and various leukemia and lymphoma cells—targeting this complex allows for the selective destruction of cancerous blood cells while sparing non-hematopoietic tissues (Griffioen et al., 2008). This specificity is particularly valuable in the context of allogeneic stem cell transplantation, where it can mediate a graft-versus-leukemia (GvL) effect with a reduced risk of systemic graft-versus-host disease (GvHD). Current therapeutic developments include TCR-engineered T-cell therapies, such as MDG1021, and peptide-based vaccines aimed at inducing a robust cytotoxic T-lymphocyte response against HA-1-positive malignant cells (Medigene AG). Clinical success depends on patient selection based on HLA-A*02:01 positivity and the presence of the HA-1H allele, providing a precision medicine approach to treating relapsed leukemia.

Other names

HMHA1 peptide–HLA-A*02:01ARHGAP45 peptide–HLA-A*02:01HA-1 mHAgVLHDDLLEA–HLA-A*02:01Minor histocompatibility antigen HA-1

T-cell receptor (TCR) mediated recognition and subsequent cytotoxic T-lymphocyte (CTL) mediated lysis of target cells.