Cognate recognition of microbial antigens defines constricted CD4+ T cell receptor repertoires in the inflamed colon

Abstract

Key aspects of intestinal Tcells, including their antigen specificity and their selection by the microbiota and other intestinal antigens, as well as the contribution of individual Tcell clones to regulatory and effector functions, remain unresolved. Here we tracked adoptively transferred Tcell populations to specify the interrelation of Tcell receptor repertoire and the gut antigenic environment. We show that dominant TCRα clonotypes were shared between interferon-γ- and interleukin-17-producing but not regulatory Foxp3+ Tcells. Identical TCRα clonotypes accumulated in the colon of different individuals, whereas antibiotics or defined colonization correlated with the expansion of distinct expanded Tcell clonotypes. Our results demonstrate key aspects of intestinal CD4+ Tcell activation and suggest that few microbial species exert a dominant effect on the intestinal Tcell repertoire during colitis. We speculate that dominant proinflammatory Tcell clones might provide a therapeutic target in human inflammatory bowel disease.