RRAS2 shapes the TCR repertoire by setting the threshold for negative selection.

ABSTRACT: Signal strength controls the outcome of αβ T cell selection in the thymus, resulting in death if the affinity of the rearranged TCR is below the threshold for positive selection, or if the affinity of the TCR is above the threshold for negative selection. Here we show that deletion of the GTPase RRAS2 results in exacerbated negative selection and above-normal expression of positive selection markers. Furthermore, Rras2^-/- mice are resistant to autoimmunity both in a model of inflammatory bowel disease (IBD) and in a model of myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE). We show that MOG-specific T cells in Rras2^-/- mice have reduced affinity for MOG/I-A^b tetramers, suggesting that enhanced n

SUBMITTER: Martinez-Riano A 

PROVIDER: S-EPMC6781009 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature