HLA-A*02:01-p14ARF (ARF35-43) complex (HLA-A*02:01/p14ARF(35-43))

The HLA-A*02:01-p14ARF (ARF35-43) complex is a peptide-major histocompatibility complex (pMHC) that serves as a tumor-associated antigen for T-cell based immunotherapies. It consists of the ARF35-43 epitope (sequence: FVRSRRPRT) presented by the HLA-A*02:01 allele. Although this specific peptide sequence was originally identified in early p14ARF literature and shares identity with the mouse p19ARF homolog, it has been extensively characterized as a target for human cytotoxic T lymphocytes in cancers where the CDKN2A locus is active (McKolanis et al., 2001, PubMed: 11544040). p14ARF is a tumor suppressor that regulates the p53 pathway, and its overexpression in certain tumors—often as a response to p53 loss—facilitates the presentation of this epitope (UniProt P42771). Therapeutic approaches primarily involve TCR-engineered T-cells (TCR-T) designed to recognize this complex with high specificity. Recognition by the TCR triggers T-cell activation, leading to the directed lysis of tumor cells. Key challenges for this target include ensuring the absence of cross-reactivity with human self-peptides and the requirement for patients to be HLA-A*02:01 positive.

Other names

p14ARF(35-43) HLA-A*02:01ARF35-43/HLA-A2 complexp14ARF-derived tumor-associated antigenp14ARF-derived epitope

T-cell receptor (TCR) mediated recognition of the peptide-MHC complex leading to cytotoxic T lymphocyte activation and tumor cell lysis.