CD4+ T regulatory and effector cells display a similar wide range of affinities for self during autoimmune disease (BA13P.129)

Abstract

Abstract The affinity of a T cell receptor (TCR) from a regulatory T cell (Treg) for endogenous self peptide MHC complex is unknown. It is thought that thymic derived Tregs (nTregs) are enriched for high affinity, self-reactive TCRs as an alternative to negative selection. During experimental autoimmune encephalomyelitis (EAE), MOG self-antigen pMHC tetramers identified few (<10%) of the infiltrating CD4+ Tregs and Teffs. The micropipette adhesion frequency assay has previously proven more sensitive for assessing TCR specificity, affinity and frequency of antigen specific cells. Using this assay, it was determined that most of the Tregs and Teffs (>80% each) localized in the central nervous system (CNS) at peak EAE are in fact MOG self antigen specific. Tregs and Teffs possessed similar broad 1000 fold ranges in affinities for MOG with geometric means of 1 and 4 X 10-5 μm4. In the CNS, greater than 90% of the Tregs expressed helios which was consistent with frequencies in the thymus (94%), which suggests an enrichment of nTregs in the CNS during peak EAE. Contrary to the hypothesis that nTregs arise as an alternative to negative selection due to a high affinity for self, our data show that TCR affinity of MOG specific Tregs mimics Teffs with no enrichment of high affinity cells.