HA-1-specific αβ T cell receptor (HA-1 TCR)

The HA-1-specific αβ T cell receptor (TCR) is a recombinant or naturally occurring immune receptor designed to recognize the minor histocompatibility antigen HA-1 (Blood, 2024). HA-1 is a polymorphic peptide (VLHDDLLEA) derived from the ARHGAP45 (formerly HMHA1) protein and is presented on the cell surface by the human leukocyte antigen (HLA) allele HLA-A*02:01 (ASH Publications, 2024). This TCR is primarily utilized in adoptive T cell therapies (TCR-T) for the treatment of hematologic malignancies, such as acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL), following allogeneic hematopoietic stem cell transplantation (HSCT) (ClinicalTrials.gov, NCT03326921). By engineering donor-derived T cells to express this specific TCR, the therapy can selectively target and eliminate recipient-derived hematopoietic cells, including malignant blasts, while sparing non-hematopoietic tissues (TScan Therapeutics, 2024). This specificity is due to the restricted expression of HA-1 in the hematopoietic system, which helps minimize the risk of graft-versus-host disease (GvHD) while promoting a potent graft-versus-leukemia (GvL) effect (Fred Hutch, 2025). Clinical candidates like TSC-100 are currently being investigated to prevent or treat disease relapse in patients undergoing transplant (NCI, 2024).

Other names

Minor histocompatibility antigen HA-1-specific T cell receptorAnti-HA-1 TCRHMHA1-specific T cell receptorHA-1-specific TCRARHGAP45-specific T cell receptor

Recognition of the HA-1 peptide (VLHDDLLEA) presented by HLA-A*02:01 on target cells, leading to T cell activation, cytokine release, and cytotoxic lysis of the target cell.