U2 small nuclear RNA auxiliary factor 1 Q157R mutant peptide presented by HLA-A*33:01 or HLA-A*33:03 (U2AF1 Q157R/HLA-A*33 complex)

The U2AF1 Q157R mutant peptide presented by HLA-A*33:01 or HLA-A*33:03 is a highly specific neoantigen complex found in myeloid malignancies. U2AF1 (U2 small nuclear RNA auxiliary factor 1) is a critical component of the spliceosome, and the Q157R mutation in its second zinc finger domain alters RNA splicing patterns, driving oncogenesis in diseases such as myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) [1][2]. Because this mutation is somatic and tumor-specific, the resulting mutant peptide can be processed and presented by specific Human Leukocyte Antigen (HLA) molecules, such as HLA-A*33:01 and HLA-A*33:03, which are prevalent in certain populations [3]. This peptide-MHC complex serves as a therapeutic target for precision immunotherapy, including TCR-engineered T-cell (TCR-T) therapies and neoantigen vaccines [4]. By targeting this complex, the immune system can be directed to selectively eliminate leukemic clones while sparing healthy cells that lack the mutation. Current research focuses on identifying high-affinity TCRs that can recognize this specific epitope without cross-reacting with the wild-type U2AF1 sequence [5]. Citations: [1] https://pubmed.ncbi.nlm.nih.gov/22080990/ [2] https://www.uniprot.org/uniprotkb/Q01081/entry [3] https://pubmed.ncbi.nlm.nih.gov/33077940/ [4] https://pubmed.ncbi.nlm.nih.gov/31160319/ [5] https://ashpublications.org/blood/article/134/Supplement_1/319/423943/Identification-of-a-U2AF1-Q157R-Neoantigen

Other names

U2AF1 Q157R neoantigenU2AF1 p.Gln157Arg peptide-MHC complexHLA-A*33:01-restricted U2AF1 Q157RHLA-A*33:03-restricted U2AF1 Q157RU2AF35 Q157R mutant peptide

Targeting of the peptide-MHC complex by engineered T-cell receptors (TCRs) or vaccine-induced cytotoxic T-lymphocytes leads to the selective recognition and lysis of malignant cells harboring the U2AF1 Q157R mutation.