HLA class I epitope discovery in type 1 diabetes: independent and reproducible identification of proinsulin epitopes of CD8 T cells--report of the IDS T Cell Workshop Committee.

Islet autoreactive CD8 T cells are plausible candidates for direct beta cell toxicity in type 1 diabetes (T1DM). In 2005, cellular studies in the pathogenesis of this disease have reached a new milestone. Autoreactive CD8 T cells have been defined and several target islet epitopes of these have been discovered and validated simultaneously in three independent studies. The insulin B10-B18 peptide that displays exceptional binding affinity for HLA-A2 has been reported in all three studies, and its recognition shows an association with autoimmune beta cell destruction and T1DM. These studies imply that CD8 T cell-based HLA tetramers and ELISPOT analyses can be useful to monitor T1DM as well as islet transplantation, and may provide useful tools to assess immunological efficacy of immune intervention trials.