Minor histocompatibility antigen UTA2-1 (UTA2-1)

Minor histocompatibility antigen UTA2-1 (UTA2-1) is a polymorphic peptide presented by the HLA-A*02:01 molecule, derived from the hematopoietic-specific protein encoded by the RESF1 (formerly C12orf35 or KIAA1551) gene. It was identified through genome-wide zygosity-genotype correlation analysis of T-cell clones from a multiple myeloma patient who experienced long-term remission after donor lymphocyte infusion. Because its expression is restricted to the hematopoietic system, UTA2-1 is considered an ideal target for immunotherapy following allogeneic stem cell transplantation (allo-SCT) to induce a graft-versus-tumor (GvT) effect without causing widespread graft-versus-host disease (GvHD). The antigen is defined by a single nucleotide polymorphism (SNP rs2166807) that results in a nonameric peptide (QLLNSVLTL) capable of eliciting a robust CD8+ cytotoxic T-lymphocyte response. Therapeutic strategies targeting UTA2-1 include dendritic cell vaccines (e.g., NCT02528682) and adoptive T-cell therapies, which aim to eliminate residual malignant hematopoietic cells in HLA-matched, mHag-mismatched transplant recipients. This target represents a promising approach for personalized cancer immunotherapy in the context of stem cell transplantation.

Other names

mHag UTA2-1C12orf35-derived antigenKIAA1551-derived antigenRESF1-derived antigenGET-derived antigen

Recognition of the UTA2-1 peptide/HLA-A*02:01 complex by CD8+ cytotoxic T lymphocytes, leading to targeted lysis of hematopoietic cells.