UTA2-1 minor histocompatibility antigen (UTA2-1)

UTA2-1 minor histocompatibility antigen (UTA2-1) is a polymorphic peptide presented by the HLA-A*02:01 molecule, derived from the Retroelement Silencing Factor 1 (RESF1) gene, formerly known as C12orf35 or KIAA1551 (Oostvogels et al., 2013; UniProt Q9HCM1). It was identified through the analysis of cytotoxic T lymphocyte (CTL) clones from a multiple myeloma patient who achieved long-term remission following donor lymphocyte infusion (DLI) (Oostvogels et al., 2013). The antigen is defined by a single nucleotide polymorphism (rs2166807) that results in the hematopoietic-restricted expression of the immunogenic nonameric peptide QLLNSVLTL (Oostvogels et al., 2013; Frontiers in Immunology, 2020). Because its expression is limited to the hematopoietic system, including malignant B and T cells, UTA2-1 is a highly attractive target for immunotherapy aimed at inducing a graft-versus-tumor (GvT) effect without causing significant graft-versus-host disease (GvHD) (Oostvogels et al., 2013; JCI, 2020). Current therapeutic strategies involving UTA2-1 include the development of peptide-loaded dendritic cell vaccines and the use of T-cell receptor (TCR) engineered T cells in the context of allogeneic stem cell transplantation (NCT02528682; NCT03326921). Its balanced population frequency and restriction to the common HLA-A*02:01 allele make it a clinically relevant target for a significant portion of the patient population (Oostvogels et al., 2013).

Other names

MiHA UTA2-1mHAg UTA2-1Minor histocompatibility antigen UTA2-1Utrecht antigen 2-1C12orf35 antigenRESF1 antigenGET antigenKIAA1551 antigen

Recognition of the peptide-MHC complex by CD8+ cytotoxic T lymphocytes leading to target cell lysis