Evidence that HLA class II-restricted human CD4+ T cells specific to p53 self peptides respond to p53 proteins of both wild and mutant forms

Hiroshi Fujita, Satoru Senju, Hiroshi Yokomizo, Hideyuki Saya, Michio Ogawa, Sho Matsushita, Yasuharu Nishimura

Research output: Contribution to journalArticle

60 Citations (Scopus)

Abstract

By stimulating peripheral blood mononuclear cells of four healthy donors with a mixture of overlapping peptides representing the core domain of p53, we established two CD4+ αβ T cell clones and four lines that recognized wild-type and mutant p53 proteins as well as p53 self peptides in an HLA class II-restricted fashion. Two T cell lines established from two unrelated donors reacted to the p53 peptide (p)153-166 and p108-122, respectively, in the context of DP5 molecules. Two T cell clones established from two other unrelated donors were specific for p193-204 in the context of DRB1*1401 and for p153-165 in the context of DP5, respectively. These two T cell clones responded almost equally to both wild-type and four mutant recombinant p53 proteins. The proliferative responses of these T cell clones to p53 recombinant proteins were augmented by heat denaturing, thereby suggesting that altered conformation of the protein facilitates proteolytic processing to produce antigenic peptides. The DRB1*1401-restricted T cell clone specific for p193-204 killed a B lymphoblastoid cell line homozygous for HLA-DRB1*1401 when the cell line was pre-pulsed with p53 protein as well as peptide. These results indicate that CD4+ T cells reactive to p53 do exist in healthy individuals and the epitopes are probably ignored by the immune system under physiological conditions. It is suggested that such epitopes stimulate T cells to induce anti-p53 antibody production in cancer patients as previously reported by others. The possible involvement of p53-reactive T cells in anti-tumor immunity is discussed.

Original languageEnglish
Pages (from-to)305-316
Number of pages12
JournalEuropean Journal of Immunology
Volume28
Issue number1
DOIs
Publication statusPublished - 1998 Jan 1
Externally publishedYes

Keywords

  • Antigen presentation
  • HLA
  • T cell
  • Tumor immunity
  • p53 tumor suppressor gene

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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