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 bre ast cancer, there is a need to identify further tumor-associated peptide ep itopes that are specific for HLA alleles, in addition to HLA-A2, The HLA-B4 4 haplotype is one of the most common HLA-B haplotypes, occurring in 10-20% of the population. We performed the structural characterization of HLA cla ss 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 an tigens, 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 t he latter peptides, FEVRVCACPG, shared 100% homology to residues 270-279 of wild-type P53 protein. Our study, thus, provides direct evidence for the n atural processing and presentation of p53 epitope 270-279 by HLA-B40, B44-b earing human breast tumor cells. Epitopes spanning this region of P53 may h ave potential use for immunotherapy in patients expressing HLA-A2 and -B44 supertypes.