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

The HA-1 minor histocompatibility antigen (mHAg) is a lineage-specific antigen derived from the HMHA1 (ARHGAP45) gene, which is predominantly expressed in hematopoietic cells, including leukemic cells (UniProt Q92619; PMID: 24086303). The specific peptide VLHDDLLEA is presented by the HLA-A*02:01 molecule and arises from a non-synonymous single nucleotide polymorphism (SNP) in the HMHA1 gene (PMID: 9445411). Because its expression is restricted to the hematopoietic system, HA-1 is a highly attractive target for immunotherapy in the context of allogeneic hematopoietic stem cell transplantation (allo-HSCT). By targeting HA-1, clinicians aim to induce a potent graft-versus-leukemia (GvL) effect while minimizing the risk of graft-versus-host disease (GvHD) in other organs (PMID: 17533392). Current therapeutic strategies include the development of TCR-engineered T cells (TCR-T), such as MDG1021, and peptide-based vaccines designed to recognize the HA-1/HLA-A*02:01 complex (NCT04464889). These therapies leverage the donor's immune system to selectively eliminate residual malignant cells in the recipient while sparing non-hematopoietic tissues.

Other names

HA-1mHAg HA-1HMHA1 peptideARHGAP45 peptideVLHDDLLEA peptideHLA-A*02:01/HA-1 complex

Targeting of the HA-1 peptide-MHC complex by engineered T-cell receptors (TCRs) or vaccines to induce selective T-cell mediated lysis of HA-1-expressing hematopoietic cells.