Bézie S., B. Charreau, N. Vimond, J. Lasselin, N. Gérard, V. Nerrière-Daguin, F. Bellier-Waast, F. Duteille, I. Anegon* and C. Guillonneau*.
2019 | Blood Adv. 3:3522.
To reduce the use of non-specific immunosuppres- sive drugs detrimental to transplant patient health, therapies in development aim to achieve antigen- specific tolerance by promoting antigen-specific reg- ulatory T cells (Tregs). However, identification of the natural antigens recognized by Tregs and the contri- bution 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-reac- tive 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. Pep- tides derived from human HLA class II molecules, harboring the rat consensus sequence, also activate and expand human CD8+ Tregs, suggesting its poten- tial 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.