Wild-type p53 epitope naturally processed and presented by an HLA-B haplotype on human breast carcinoma cells

Clin Cancer Res. 1999 Aug;5(8):2089-93.

Abstract

To broaden the clinical applicability of peptide-based immunotherapy in breast cancer, there is a need to identify further tumor-associated peptide epitopes that are specific for HLA alleles, in addition to HLA-A2. The HLA-B44 haplotype is one of the most common HLA-B haplotypes, occurring in 10-20% of the population. We performed the structural characterization of HLA class I-bound self-peptides presented by a human breast cancer cell line with a HLA-A68, A32, B40, B44 haplotype, to identify potential tumor-specific antigens. Of 13 sequenced peptides, 1 peptide had the HLA-A68 peptide binding motif and 12 peptides had the HLA-B40, B44 peptide binding motif. One of the latter peptides, FEVRVCACPG, shared 100% homology to residues 270-279 of wild-type P53 protein. Our study, thus, provides direct evidence for the natural processing and presentation of p53 epitope 270-279 by HLA-B40, B44-bearing human breast tumor cells. Epitopes spanning this region of P53 may have potential use for immunotherapy in patients expressing HLA-A2 and -B44 supertypes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / immunology*
  • Amino Acid Sequence
  • Antigen Presentation / immunology*
  • Breast Neoplasms / immunology*
  • Chromatography, High Pressure Liquid
  • Epitopes / immunology
  • Female
  • Fluorescent Antibody Technique, Direct
  • HLA-B Antigens / chemistry
  • HLA-B Antigens / immunology*
  • Haplotypes / immunology
  • Histocompatibility Antigens Class I / chemistry
  • Histocompatibility Antigens Class I / immunology
  • Humans
  • Immunophenotyping
  • Peptide Fragments / chemistry
  • Peptide Fragments / immunology
  • Sequence Analysis
  • Tumor Cells, Cultured
  • Tumor Suppressor Protein p53 / immunology*

Substances

  • Epitopes
  • HLA-B Antigens
  • Histocompatibility Antigens Class I
  • Peptide Fragments
  • Tumor Suppressor Protein p53