Efficient Presentation of Multiple Endogenous Epitopes to Both CD4⁺ and CD8⁺ Diabetogenic T Cells for Tolerance.

ABSTRACT: Antigen-specific immunotherapy of type 1 diabetes, typically via delivery of a single native β cell antigen, has had little clinical benefit to date. With increasing evidence that diabetogenic T cells react against multiple β cell antigens, including previously unappreciated neo-antigens that can be emulated by mimotopes, a shift from protein- to epitope-based therapy is warranted. To this end, we aimed to achieve efficient co-presentation of multiple major epitopes targeting both CD4⁺ and CD8⁺ diabetogenic T cells. We have compared native epitopes versus mimotopes as well as various targeting signals in an effort to optimize recognition by both types of T cells in vitro. Optimal engagement of all T cells was achieved with segregation of CD8 and CD4 epitopes, the latt

SUBMITTER: Dastagir SR 

PROVIDER: S-EPMC5363322 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature