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
相关论文
共 39 条
[1]  
Barfoed AM, 2000, SCAND J IMMUNOL, V51, P128
[2]   Cytotoxic T lymphocyte responses to wild-type and mutant mouse p53 peptides [J].
Bertholet, S ;
Iggo, R ;
Corradin, G .
EUROPEAN JOURNAL OF IMMUNOLOGY, 1997, 27 (03) :798-801
[3]   Loss of function and p53 protein stabilization [J].
Blagosklonny, MV .
ONCOGENE, 1997, 15 (16) :1889-1893
[4]   THE SPECIFICITY OF RECOGNITION OF A CYTOTOXIC LYMPHOCYTE-T EPITOPE [J].
BURROWS, SR ;
RODDA, SJ ;
SUHRBIER, A ;
GEYSEN, HM ;
MOSS, DJ .
EUROPEAN JOURNAL OF IMMUNOLOGY, 1992, 22 (01) :191-195
[5]  
Busch DH, 1998, J IMMUNOL, V160, P4441
[6]  
Caron De Fromentel Claude, 1992, Genes Chromosomes and Cancer, V4, P1
[7]  
Chikamatsu K, 1999, CLIN CANCER RES, V5, P1281
[8]   ANALYSIS OF PHYSICAL INTERACTIONS BETWEEN PEPTIDES AND HLA MOLECULES AND APPLICATION TO THE DETECTION OF HUMAN IMMUNODEFICIENCY VIRUS-1 ANTIGENIC PEPTIDES [J].
CHOPPIN, J ;
MARTINON, F ;
GOMARD, E ;
BAHRAOUI, E ;
CONNAN, F ;
BOUILLOT, M ;
LEVY, JP .
JOURNAL OF EXPERIMENTAL MEDICINE, 1990, 172 (03) :889-899
[9]   p53-based immunotherapy of cancer [J].
DeLeo, AB .
CRITICAL REVIEWS IN IMMUNOLOGY, 1998, 18 (1-2) :29-35
[10]   An HLA-B35-restricted epitope modified at an anchor residue results in an antagonist peptide [J].
Dong, T ;
Boyd, D ;
Rosenberg, W ;
Alp, N ;
Takiguchi, M ;
McMichael, A ;
RowlandJones, S .
EUROPEAN JOURNAL OF IMMUNOLOGY, 1996, 26 (02) :335-339