Minor histocompatibility antigen HA-2 peptide in complex with Human Leukocyte Antigen A*02:01 (HA-2/HLA-A*02:01)

The HA-2 peptide in complex with HLA-A*02:01 is a well-characterized minor histocompatibility antigen (mHAg) complex that plays a crucial role in the immunology of allogeneic hematopoietic stem cell transplantation (Goulmy, 1997, Hum Immunol). The HA-2 peptide, with the sequence YIGEVLVSV, is derived from the MYO1G gene (encoding Myosin IG) and is presented specifically by the HLA-A*02:01 MHC class I molecule (Pierce et al., 2001, Science). This peptide-MHC complex is a primary target for cytotoxic T lymphocytes (CTLs) in the context of the Graft-versus-Leukemia (GvL) effect, where donor-derived T cells recognize and eliminate recipient leukemic cells (Mutis et al., 1999, Blood). Because MYO1G expression is largely restricted to hematopoietic cells, targeting the HA-2/HLA-A*02:01 complex is considered a promising strategy for immunotherapy with a lower risk of systemic Graft-versus-Host Disease (GvHD) compared to other antigens. Current therapeutic approaches include the use of TCR-engineered T cells and peptide vaccines designed to selectively boost the immune response against HA-2-positive malignant cells. However, clinical application requires careful patient and donor screening for the appropriate HLA type and HA-2 polymorphism status to ensure therapeutic efficacy and safety.

Other names

HA-2/HLA-A2 complexMYO1G peptide/HLA-A*02:01mHAg HA-2YIGEVLVSV/HLA-A*02:01Minor histocompatibility antigen HA-2

The complex is recognized by specific T-cell receptors (TCRs) on CD8+ cytotoxic T lymphocytes, which triggers the release of perforins and granzymes to induce apoptosis in the target cell (Mutis et al., 1999, Blood).