U2 small nuclear RNA auxiliary factor 1 Q157R mutant peptide presented by Human leukocyte antigen A*33 (U2AF1 Q157R/HLA-A*33)

The U2AF1 Q157R mutant peptide presented by Human leukocyte antigen A*33 is a tumor-specific neoantigen complex that serves as a target for precision immunotherapy in myeloid malignancies. U2AF1 (U2 small nuclear RNA auxiliary factor 1) is a splicing factor that recognizes the AG dinucleotide at the 3' splice site; mutations like Q157R alter its RNA-binding specificity, leading to widespread splicing dysregulation (UniProt P23588; Graubert et al., 2012, Nature Genetics). The Q157R mutation is a recurrent somatic event in myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML), creating a unique amino acid sequence that is processed into neoantigenic peptides (Yoshida et al., 2011, Nature). These peptides are presented on the cell surface by specific Human Leukocyte Antigen (HLA) alleles, such as HLA-A*33, making the malignant cells visible to the cellular immune system (NCI Thesaurus). Therapeutic strategies targeting this complex include TCR-engineered T-cell (TCR-T) therapies and neoantigen vaccines, which aim to elicit a cytotoxic T-lymphocyte response specifically against the mutation-bearing cells (PubMed: 32814731). This target is highly attractive due to its tumor-exclusivity, which potentially reduces the risk of off-target toxicity compared to traditional chemotherapy.

Other names

U2AF1 Q157R neoantigenHLA-A*33-restricted U2AF1 Q157R peptideU2AF1-Q157R/HLA-A*33:03 complexU2AF1 Q157R/MHC class I complex

T-cell mediated lysis of cells expressing the U2AF1 Q157R mutation via TCR recognition of the peptide-MHC complex.