title: Identification of a naturally processed HLA-A*02:01-restricted CTL epitope from the human tumor-associated antigen Nectin-4.
abstract: Nectin-4 is a tumor antigen present on the surface of breast, ovarian and lung carcinoma cells. It is rarely present in normal adult tissues and is therefore a candidate target for cancer immunotherapy. Here, we identified a Nectin-4 antigenic peptide that is naturally presented to T cells by HLA-A2 molecules. We first screened the 502 nonamer peptides of Nectin-4 (510 amino acids) for binding to and off-rate from eight different HLA class I molecules. We then combined biochemical, cellular and algorithmic assays to select 5 Nectin-4 peptides that bound to HLA-A*02:01 molecules. Cytolytic T lymphocytes were obtained from healthy donors, that specifically lyzed HLA-A2(+) cells pulsed with 2 out of the 5 peptides, indicating the presence of anti-Nectin-4 CD8(+) T lymphocytes in the human T cell repertoire. Finally, an HLA-A2-restricted cytolytic T cell clone derived from a breast cancer patient recognized peptide Nectin-4145-153 (VLVPPLPSL) and lyzed HLA-A2(+) Nectin-4(+) breast carcinoma cells. These results indicate that peptide Nectin-4145-153 is naturally processed for recognition by T cells on HLA-A2 molecules. It could be used to monitor antitumor T cell responses or to immunize breast cancer patients.
authors: Inserm U1068, Centre de Recherche en Cancérologie de Marseille (CRCM), Equipe Oncologie Moléculaire, UM 105, Institut Paoli-Calmettes, CNRS, UMR7258, Aix-Marseille University, Marseille, France.
authors: Marc
authors: M
authors: Lopez
authors: Inserm U1068, Centre de Recherche en Cancérologie de Marseille (CRCM), Equipe Immunité et Cancer, UM 105, Institut Paoli-Calmettes, CNRS, UMR7258, Aix-Marseille University, 27 bd Lei Roure, 13009, Marseille, France.
authors: Abderrezak
authors: A
authors: Ghidouche
authors: Inserm U1068, Centre de Recherche en Cancérologie de Marseille (CRCM), Equipe Immunité et Cancer, UM 105, Institut Paoli-Calmettes, CNRS, UMR7258, Aix-Marseille University, 27 bd Lei Roure, 13009, Marseille, France.
authors: Caroline
authors: C
authors: Rochas
authors: Ludwig Institute for Cancer Research, Brussels Branch, Brussels, Belgium.|de Duve Institute, Université catholique de Louvain, Brussels, Belgium.
authors: Danièle
authors: D
authors: Godelaine
authors: Department of Oncology and Hematology, Grand Hôpital de Charleroi, Charleroi, Belgium.
authors: Javier
authors: J
authors: Carrasco
authors: Ludwig Institute for Cancer Research, Brussels Branch, Brussels, Belgium.|de Duve Institute, Université catholique de Louvain, Brussels, Belgium.
authors: Didier
authors: D
authors: Colau
authors: de Duve Institute, Université catholique de Louvain, Brussels, Belgium.
authors: Gérald
authors: G
authors: Hames
authors: bioMérieux Industry, Ivry sur Seine, France.
authors: Félix A
authors: FA
authors: Montero-Julian
authors: de Duve Institute, Université catholique de Louvain, Brussels, Belgium.
authors: Pierre G
authors: PG
authors: Coulie
authors: Inserm U1068, Centre de Recherche en Cancérologie de Marseille (CRCM), Equipe Immunité et Cancer, UM 105, Institut Paoli-Calmettes, CNRS, UMR7258, Aix-Marseille University, 27 bd Lei Roure, 13009, Marseille, France. daniel.olive@inserm.fr.
authors: Daniel
authors: D
authors: Olive
mesh_terms: D000230:Adenocarcinoma / Q000276:immunology*; D000951:Antigens, Neoplasm / Q000276:immunology; D001943:Breast Neoplasms / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology*; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D045744:Cell Line, Tumor; D002999:Clone Cells; D018604:Epitope Mapping; D018984:Epitopes, T-Lymphocyte / Q000378:metabolism*; D005260:Female; D015789:HLA-A2 Antigen / Q000378:metabolism; D006801:Humans; D007136:Immunoglobulins / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism*; D011485:Protein Binding; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
chemical_list: D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D015815:Cell Adhesion Molecules; D018984:Epitopes, T-Lymphocyte; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; C498602:Igsf4c protein, mouse; D007136:Immunoglobulins; D010455:Peptides
keywords: CTL; Epitope; MHC class I; Nectin-4; Tumor vaccine; Tumor-associated antigen