Autoimmune susceptibility imposed by public TCR? chains.

ABSTRACT: Although the TCR repertoire is highly diverse, a small fraction of TCR chains, referred to as public, preferentially form and are shared by most individuals. Prior studies indicated that public TCR? may be preferentially deployed in autoimmunity. We hypothesized that if these TCR? modulate the likelihood of a TCR?? heterodimer productively engaging autoantigen, because they are widely present in the population and often high frequency within individual repertoires, they could also broadly influence repertoire responsiveness to specific autoantigens. We assess this here using a series of public and private TCR? derived from autoimmune encephalomyelitis-associated TCR. Transgenic expression of public, but not private, disease-associated TCR? paired with endogenously rearranged TCR? endowed unprimed T cells with autoantigen reactivity. Further, two of six public, but none of five private TCR? provoked spontaneous early-onset autoimmunity in mice. Our findings indicate that single TCR? are sufficient to confer on TCR?? chains reactivity toward disease-associated autoantigens in the context of diverse TCR?. They further suggest that public TCR can skew autoimmune susceptibility, and that subsets of public TCR sequences may serve as disease- specific biomarkers or therapeutic targets.

SUBMITTER: Zhao Y 

PROVIDER: S-EPMC5116635 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature