PMID: 7543215Jul 1, 1995Paper

T cell-mediated cytotoxicity against p53-protein derived peptides in bulk and limiting dilution cultures of healthy donors

Scandinavian Journal of Immunology
M RöpkeM H Claesson

Abstract

The p53 tumour suppressor gene product plays an important role in the development of most human cancers. Point mutations in the p53 gene are common in malignant states and results in over-expression of wild type and mutant determinants of the p53 protein. This process might generate MHC-I restricted epitopes for T cell recognition and p53-derived peptides have been suggested as targets for tumour-specific cytotoxic T lymphocytes (CTL). Our primary aim was to estimate the frequencies of p53-peptide reactive CTL precursors (CTLp) in peripheral blood from healthy young individuals. We selected wild type and mutated peptides derived from the p53 sequence with a binding motif for HLA-A2.1 molecules. Peripheral blood mononuclear cells (PBMC) from healthy HLA-A2 donors were stimulated in vitro in bulk cultures as well as in limiting dilution cultures using autologous cells pulsed with p53 peptides as stimulator cells. T cell reactivity was observed towards both wild type and mutated p53 peptide epitopes with CTL precursor frequencies varying from 1:2 x 10(4) to 1:1.5 x 10(5). These results might suggest the presence of an ongoing immune response in normal individuals against cells expressing increased levels of p53 protein.

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Citations

Aug 24, 2001·International Journal of Cancer. Journal International Du Cancer·P A WürtzenM H Claesson
Jun 26, 2010·Cancer Immunology, Immunotherapy : CII·Pedro A Andrade FilhoRobert L Ferris
Nov 22, 1997·Current Opinion in Immunology·U SahinM Pfreundschuh
Apr 1, 1997·Molecular Medicine Today·H L Chen, D P Carbone
Sep 17, 2005·Journal of Translational Medicine·H W NijmanT Daemen
Dec 10, 1996·Proceedings of the National Academy of Sciences of the United States of America·M RöpkeM H Claesson
May 7, 2002·International Journal of Cancer. Journal International Du Cancer·Peter A Würtzen, Mogens H Claesson
Mar 1, 1997·European Journal of Immunology·S BertholetG Corradin
Dec 5, 2000·International Journal of Cancer. Journal International Du Cancer·K YamaguchiD Sidransky
Feb 10, 1998·International Journal of Cancer. Journal International Du Cancer·K ZekiS Eto
Nov 9, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·T K HoffmannA B DeLeo

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