Heparan Sulfate Proteoglycans Promote Telomerase Internalization and MHC Class II Presentation on Dendritic Cells.
Fiche publication
Date publication
septembre 2016
Journal
Journal of immunology (Baltimore, Md. : 1950)
Auteurs
Membres identifiés du Cancéropôle Est :
Pr ADOTEVI Olivier, Dr BOIDOT Romain, Pr BORG Christophe, Dr GODET Yann, Dr MANSI Laura, Dr GALAINE Jeanne, Dr LOYON Romain
Tous les auteurs :
Galaine J, Kellermann G, Guillaume Y, Boidot R, Picard E, Loyon R, Queiroz L, Boullerot L, Beziaud L, Jary M, Mansi L, André C, Lethier L, Ségal-Bendirdjian E, Borg C, Godet Y, Adotévi O
Lien Pubmed
Résumé
Telomerase is a prototype-shared tumor Ag and represents an attractive target for anticancer immunotherapy. We have previously described promiscuous and immunogenic HLA-DR-restricted peptides derived from human telomerase reverse transcriptase (hTERT) and referred as universal cancer peptide (UCP). In nonsmall cell lung cancer, the presence of spontaneous UCP-specific CD4 T cell responses increases the survival of chemotherapy-responding patients. However, the precise mechanisms of hTERT's uptake, processing, and presentation on MHC-II molecules to stimulate CD4 T cells are poorly understood. In this work, by using well-characterized UCP-specific CD4 T cell clones, we showed that hTERT processing and presentation on MHC-II involve both classical endolysosomal and nonclassical cytosolic pathways. Furthermore, to our knowledge, we demonstrated for the first time that hTERT's internalization by dendritic cells requires its interaction with surface heparan sulfate proteoglycans. Altogether, our findings provide a novel mechanism of tumor-specific CD4 T cell activation and will be useful for the development of novel cancer immunotherapies that harness CD4 T cells.
Mots clés
Antigen Presentation, CD4-Positive T-Lymphocytes, immunology, Cell Line, Tumor, Dendritic Cells, immunology, Epitopes, T-Lymphocyte, immunology, HLA-DR Antigens, immunology, Heparan Sulfate Proteoglycans, metabolism, Humans, Immunotherapy, Lymphocyte Activation, Monocytes, Peptides, metabolism, Telomerase, immunology
Référence
J. Immunol.. 2016 Sep;197(5):1597-608