Heparan Sulfate Proteoglycans Promote Telomerase Internalization and MHC Class II Presentation on Dendritic Cells

Jeanne Galaine 1, 2 Guillaume Guillaume 3 Yves Guillaume 4 Romain Boidot 5 Emilie Picard 2, 1 Romain Loyon 2, 1 Lise Queiroz 6, 2 Laura Boullerot 2 Laurent Beziaud 2, 1 Marine Jary 7, 2, 1 Laura Mansi 7, 2, 1 Claire André 4 Lydie Lethier 4 Evelyne Ségal-Bendirdjian 8, 3 Christophe Borg 7, 2, 1 Yann Godet 2, 1, * Olivier Adotévi 7, 2, 1, *
* Auteur correspondant
1 LCE - Laboratoire Chrono-environnement - UFC (UMR 6249)
2 Inserm UMR 1098
3 U1007 - Homéostasie cellulaire et cancer - Reprogrammation des réponses biologiques et thérapies alternatives
4 Laboratoire de Chimie Analytique Bioanalytique et Physique [CHU Besançon]
5 Chimiothérapie et réponse immunitaire anti-tumorale (U866, Cancer, équipe 1)
LNC - Lipides - Nutrition - Cancer (U866)
6 CICB - Centre d'Investigation Clinique de Besançon
7 Service d'Oncologie Médicale [CHRU Besançon]
8 UPD5 - Université Paris Descartes - Paris 5
Abstract : 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.
Keywords : cd4(+) t-cells Antitumor immune-responses Direct tumor recognition Cancer Htert Expression Identification IFN-gamma
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https://hal-univ-bourgogne.archives-ouvertes.fr/hal-01407427
Contributeur : Lnc - Université de Bourgogne <>
Soumis le : vendredi 2 décembre 2016 - 10:22:15
Dernière modification le : vendredi 24 janvier 2020 - 07:54:05

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UNIV-BOURGOGNE | CNRS | UNIV-FCOMTE | UNIV-PARIS5 | USPC | LNC-UMR866 | CHRONO-ENVIRONNEMENT | UMR866-EQUIPE1

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Jeanne Galaine, Guillaume Guillaume, Yves Guillaume, Romain Boidot, Emilie Picard, et al.. Heparan Sulfate Proteoglycans Promote Telomerase Internalization and MHC Class II Presentation on Dendritic Cells. Journal of Immunology, Publisher : Baltimore : Williams & Wilkins, c1950-. Latest Publisher : Bethesda, MD : American Association of Immunologists, 2016, 197 (5), pp.1597 - 1608. ⟨10.4049/jimmunol.1502633⟩. ⟨hal-01407427⟩

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