Cross-Reactive Donor-Specific CD8+ Tregs Efficiently Prevent Transplant Rejection
| Autor: | Picarda, Elodie, Bézie, Séverine, Usero, Lorena, Ossart, Jason, Besnard, Marine, Halim, Hanim, Echasserieau, Klara, Usal, Claire, Rossjohn, Jamie, Bernardeau, Karine, Gras, Stéphanie, Guillonneau, Carole |
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| Přispěvatelé: | Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Institut de transplantation urologie-néphrologie (ITUN), Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), LabEX IGO Immunothérapie Grand Ouest, Monash University [Clayton], Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), Cardiff University, Nantes Metropole and the Pays de la Loire Region. This work was supported by an ESOT Junior Basic Science Grant, a Marie Curie fellowship from the 6th FP of the EU, and an Etoiles Montantes from Pays de la Loire to C.G. E.P. was supported by an INSERM-Region Pays de la Loire Fellowship, J.O. was supported by the Fondation pour la Recherche Médicale (PLP20141031245), and J.R. is supported by an ARC Laureate Fellowship. S.G. is a Monash Senior Research Fellow., Nantes Université (Nantes Univ), Le Bihan, Sylvie |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: | |
| Zdroj: | Cell Reports Cell Reports, Elsevier Inc, 2019, 29 (13), pp.4245-4255.e6. ⟨10.1016/j.celrep.2019.11.106⟩ Cell Reports, Vol 29, Iss 13, Pp 4245-4255.e6 (2019) Cell Reports, 2019, 29 (13), pp.4245-4255.e6. ⟨10.1016/j.celrep.2019.11.106⟩ |
| ISSN: | 2211-1247 |
| Popis: | Summary: To reduce the use of non-specific immunosuppressive drugs detrimental to transplant patient health, therapies in development aim to achieve antigen-specific tolerance by promoting antigen-specific regulatory T cells (Tregs). However, identification of the natural antigens recognized by Tregs and the contribution of their dominance in transplantation has been challenging. We identify epitopes derived from distinct major histocompatibility complex (MHC) class II molecules, sharing a 7-amino acid consensus sequence positioned in a central mobile section in complex with MHC class I, recognized by cross-reactive CD8+ Tregs, enriched in the graft. Antigen-specific CD8+ Tregs can be induced in vivo with a 16-amino acid-long peptide to trigger transplant tolerance. Peptides derived from human HLA class II molecules, harboring the rat consensus sequence, also activate and expand human CD8+ Tregs, suggesting its potential in human transplantation. Altogether, this work should facilitate the development of therapies with peptide epitopes for transplantation and improve our understanding of CD8+ Treg recognition. : Picarda et al. describe MHC class II-derived peptides recognized by cross-reactive CD8+ Tregs instrumental for tolerance induction in transplantation between an incompatible donor and recipient. Keywords: transplantation, tolerance, peptide, CD8+, rat, human, therapy, regulation, antigen-specific |
| Databáze: | OpenAIRE |
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