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 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.
Ferriès
E
E
INSERM U445, Laboratoire Associé No9 du Comité de Paris de la Ligue contre le Cancer, Institut Cochin de Génétique Moléculaire, Université René Descartes, Paris, France. ferries@cochin.inserm.fr
Connan
F
F
Pagès
F
F
Gaston
J
J
Hagnéré
A M
AM
Vieillefond
A
A
Thiounn
N
N
Guillet
J
J
Choppin
J
J
D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D018984:Epitopes, T-Lymphocyte / Q000276:immunology / Q000378:metabolism; D015234:HLA-A Antigens / Q000276:immunology / Q000378:metabolism; D015789:HLA-A2 Antigen / Q000276:immunology / Q000378:metabolism; D059871:HLA-A24 Antigen; D015235:HLA-B Antigens / Q000276:immunology / Q000378:metabolism; D059949:HLA-B51 Antigen; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation; D010455:Peptides / Q000276:immunology* / Q000378:metabolism; D011485:Protein Binding; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry / Q000276:immunology*; D001749:Urinary Bladder Neoplasms / Q000276:immunology* / Q000628:therapy
D018984:Epitopes, T-Lymphocyte; D015234:HLA-A Antigens; D015789:HLA-A2 Antigen; D059871:HLA-A24 Antigen; D015235:HLA-B Antigens; D059949:HLA-B51 Antigen; D015395:Histocompatibility Antigens Class I; D010455:Peptides; D016159:Tumor Suppressor Protein p53