Identification of p53 peptides recognized by CD8(+) T lymphocytes from patients with bladder cancer

In many types of cancer, p53 frequently accumulates in tumor cells and anti -p53 antibodies can be detected. However, only four CD8(+) T-cell epitopes from p53 have been identified in humans so far. To further analyze the deve lopment of a T-cell response against p53, peptides having binding motifs sp ecific for HLA-A1, -A2, -A3, -A24, -B7, -B35, -B44, and -B51 molecules have been defined. The HLA-binding capacity of those peptides was tested, and t he stability of formed complexes was defined. Thirteen peptides that bound to HLA-A24 and -B44 molecules are presented. The positive peptides were the n used to detect the anti-p53 response of CD8+ T lymphocytes from patients with bladder cancer. Six peptides, presented by HLA-A2, -B51, or -A24, were able to stimulate T cells from two patients (among 16) with tumor cells th at strongly accumulated p53. On the contrary, p53 peptides systematically f ailed to stimulate T cells from healthy donors or patients with low or unde tectable levels of p53 in their tumor cells. These results have led to the identification of four new potential T CD8+ epitopes from p53: 194-203 asso ciating with HLA-B51 and 204-212, 211-218, and 235-243 associating with HLA -A24. Human Immunology 62, 791-798 (2001), (C) American Society for Histoco mpatibility and Immunogenetics, 2001. Published by Elsevier Science Inc.