A Novel Approach of T Cell Receptor Classification Reveals Dynamic Interactions Amongst Diet, Microbiota, and Host T Cells

The intestinal immune system is adapted to maintain constant interactions with environmental stimuli without causing inflammation. The recognition of Ags derived from microbes and diet can induce Treg or effector T cell responses through dynamic regulatory mechanisms, significantly impacting host health and disease. Although several examples of Ag-specific T cell responses to microbial or dietary Ags have been reported, our understanding of the full range of gut T cell responses remains highly limited. In this review, we highlight recent insights into the complexity of gut TCR responses. Different from traditional approaches, such as TCR transgenic mice and peptide MHC tetramers, our novel approach enables comprehensive analysis of entire repertoire of intestinal TCR responses, revealing both aggregated or individual TCR responses to different classes of Ags, which are regulated by bidirectional interactions between diet and microbiota.