Description

Detection of Wildtype p53_124-134/HLA-A*24:02 Complexes Presented by Tumour Cell Lines Expressing Mutant p53 with a T Cell Receptor-like Antibody

Jianrong Lionel LOW¹, Angeline Xi-Hua Goh¹, Joanna KOH, Samantha LIM, Cheng-I WANG

Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), Singapore

¹Both authors contributed equally to the work.

The tumor suppressor p53 is one of the most commonly mutated genes found in a wide range of cancers. Such mutations are associated with protein accumulation and increased presentation of p53-derived peptides on the surface of tumor cells as pMHCs that are recognized by specific CD8⁺ T cells. The p53 peptide 125–134 (p53_125-134) was previously described as a wild-type sequence p53 derived peptide restricted by the MHC class I allele HLA-A*24:02, capable of activating peptide specific CD8⁺ cytotoxic T cells from peripheral blood mononuclear cells (PBMCs). Utilizing a TCR-like antibody that recognizes the p53_125-134/HLA-A24 peptide MHC complex, we show that both in vitro and in vivo, p53_125-134/HLA-A24 complexes can be detected on the surface of HLA-A24⁺ tumour cells that express mutant p53, thus validating the p53_125-134/HLA-A24 as a physiologically relevant target for immunotherapy.