Cross-Reactive Donor-Specific CD8+ Tregs Efficiently Prevent Transplant Rejection

Elodie Picarda, Séverine Bézie, Lorena Usero, Jason Ossart, Marine Besnard, Hanim Halim, Klara Echasserieau, Claire Usal, Jamie Rossjohn, Karine Bernardeau, Stéphanie Gras, Carole Guillonneau

Research output: Contribution to journalArticleResearchpeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)4245-4255
Number of pages11
JournalCell Reports
Volume29
Issue number13
DOIs
Publication statusPublished - 24 Dec 2019

Keywords

  • antigen-specific
  • CD8
  • human
  • peptide
  • rat
  • regulation
  • therapy
  • tolerance
  • transplantation

Cite this

Picarda, E., Bézie, S., Usero, L., Ossart, J., Besnard, M., Halim, H., Echasserieau, K., Usal, C., Rossjohn, J., Bernardeau, K., Gras, S., & Guillonneau, C. (2019). Cross-Reactive Donor-Specific CD8+ Tregs Efficiently Prevent Transplant Rejection. Cell Reports, 29(13), 4245-4255. https://doi.org/10.1016/j.celrep.2019.11.106