Wild-type p53 epitope naturally processed and presented by an HLA-B haplotype on human breast carcinoma cells.
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.
Papadopoulos
K P
KP
Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA.
Hesdorffer
C S
CS
Suciu-Foca
N
N
Hibshoosh
H
H
Harris
P E
PE
D000230:Adenocarcinoma / Q000276:immunology*; D000595:Amino Acid Sequence; D017951:Antigen Presentation / Q000276:immunology*; D001943:Breast Neoplasms / Q000276:immunology*; D002851:Chromatography, High Pressure Liquid; D000939:Epitopes / Q000276:immunology; D005260:Female; D019085:Fluorescent Antibody Technique, Direct; D015235:HLA-B Antigens / Q000737:chemistry / Q000276:immunology*; D006239:Haplotypes / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000737:chemistry / Q000276:immunology; D006801:Humans; D016130:Immunophenotyping; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology; D017421:Sequence Analysis; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000276:immunology*
D000939:Epitopes; D015235:HLA-B Antigens; D015395:Histocompatibility Antigens Class I; D010446:Peptide Fragments; D016159:Tumor Suppressor Protein p53