Mapping and ranking of potential cytotoxic T epitopes in the p53 protein: effect of mutations and polymorphism on peptide binding to purified and refolded HLA molecules

European Journal of Immunology
Sacha GnjaticJ Choppin

Abstract

In many cancer cells, the p53 gene displays point mutations that result in stabilization and accumulation of the p53 protein. Therefore, p53 peptides could be presented to the immune system by tumor cells; thus, p53 might be a suitable target antigen for developing an immunotherapy against tumors using cytotoxic T lymphocytes (CTL). To map candidate CTL epitopes, we synthesized 150 peptides of 8-11 residues that contained putative anchor motifs required for binding to common HLA class I molecules. They were tested for their capacity to promote the assembly of purified and refolded HLA-A1, A2, B7 and B8 molecules. The following wild-type p53 peptides were found to be reactive with the HLA molecules tested: 196-205 and 226-234 bound moderately to HLA-A1; 25-35, 65-73, 129-137, 187-197, 263-272 and 264-272 bound strongly, and 187-195 and 256-264 moderately to HLA-A2; 26-35, 63-73, 189-197, 249-257 and 321-330 bound strongly to HLA-B7; and 135-143, 210-218 and 375-383 bound weakly to HLA-B8. We also analyzed the effects of p53 mutations occurring naturally in tumors on peptide/HLA assembly. We found substitutions that enhanced, diminished or had no effect on the peptide binding to HLA molecules. Polymorphism at position 72 mainly a...Continue Reading

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Citations

Sep 10, 2005·Cancer Immunology, Immunotherapy : CII·Barbara L F KaplanMichael I Nishimura
Sep 16, 2003·Journal of Immunological Methods·Rachel Bras-GonçalvesJean-Gérard Guillet
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Feb 11, 2014·Journal of Immunological Methods·Shufeng WangYuzhang Wu
Nov 1, 1996·European Journal of Immunology·V LacabanneJ Choppin
Oct 18, 2005·The British Journal of Dermatology·A P BlackG S Ogg
May 9, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·J ChoppinJ G Guillet
Jun 16, 2021·Molecular & Cellular Proteomics : MCP·Jens FritscheToni Weinschenk

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