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

The HA-1–specific T-cell receptor (TCR) is an engineered immune receptor designed to recognize the minor histocompatibility antigen HA-1 when presented by the HLA-A*02:01 major histocompatibility complex [1][2]. HA-1 is a lineage-specific antigen derived from the HMHA1 (ARHGAP45) gene, with expression primarily restricted to hematopoietic cells, including leukemic blasts [2][4]. The TCR specifically targets the VLHDDLLEA peptide, which is a product of the immunogenic 'H' allele of the HMHA1 polymorphism [1][3]. This receptor is the core component of TCR-engineered T-cell (TCR-T) therapies, such as KITE-718, which are developed to treat relapsed hematologic malignancies after allogeneic stem cell transplantation [3][6]. By specifically targeting HA-1, these TCR-T cells can induce a potent graft-versus-leukemia effect while minimizing the risk of systemic graft-versus-host disease, as the antigen is not expressed on non-hematopoietic tissues [4][5]. Upon engagement with the HA-1/HLA-A*02:01 complex, the TCR triggers T-cell activation and the subsequent lysis of the target leukemic cells [5].

Other names

HA-1-specific CD8+ T-cell receptorHLA-A*02:01/HA-1-restricted TCRHMHA1-specific TCRMinor histocompatibility antigen HA-1-specific receptor

Engineered T-cell receptors bind specifically to the HA-1 peptide (VLHDDLLEA) presented by HLA-A*02:01 on hematopoietic cells, leading to T-cell activation and cytotoxic destruction of the target cells.