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

被引:23
作者
Ferriès, E
Connan, F
Pagès, F
Gaston, J
Hagnéré, AM
Vieillefond, A
Thiounn, N
Guillet, JG
Choppin, J
机构
[1] Hop Cochin, Urol Clin, F-75014 Paris, France
[2] Hop Cochin, Serv Anat & Cytol Pathol, F-75014 Paris, France
[3] Univ Paris 05, Lab Immunol Pathol Infect & Tumorales, Paris, France
[4] Univ Paris 05, Inst Cochin Genet Mol, Comite Paris Ligue Contre Canc,Lab Associe 9, INSERM,U445, Paris, France
基金
澳大利亚研究理事会;
关键词
p53; epitopes; HLA/peptide complexes; CD8(+) T lymphocytes; bladder cancer; immunotherapy;
D O I
10.1016/S0198-8859(01)00266-X
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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 development of a T-cell response against p53, peptides having binding motifs specific 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 the stability of formed complexes was defined. Thirteen peptides that bound to HLA-A24 and -B44 molecules are presented. The positive peptides were then 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 that strongly accumulated p53. On the contrary, p53 peptides systematically failed to stimulate T cells from healthy donors or patients with low or undetectable 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 associating 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 Histocompatibility and Immunogenetics, 2001. Published by Elsevier Science Inc.
引用
收藏
页码:791 / 798
页数:8
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