The Nucleotide‐binding Oligomerisation Domain Protein 1 in T cells Modulates TCR Mediated Responses in the Thymus and Periphery

The Nucleotide‐binding oligomerisation domain protein 1 (NOD1), which functions as an intracellular sensor of bacteria, has been shown to have roles in both innate and adaptive immune responses. However, it is still unknown that T cell expression of NOD1 impacts T cell development and activation. Here we demonstrate that T cell expression of NOD1 restricts the sensitivity of T cells to TCR triggering and participates in the intra‐thymic differentiation of T cells and their proliferation in the periphery. When NOD1 is absent there is an increased commitment to the CD4 T cell lineage in the thymus and a skewed CD4 vs CD8 T cell ratios in the periphery, a phenomenon more notable after infection with either virus or bacteria. In addition, NOD1 deficient CD8 T cells exhibit increased proliferation and activation in response to antigen challenge in vitro and in vivo. Our study supports an immunoregulatory role for NOD1 expressed in T cells in the development and maintenance of a fit adaptive immune system.