Genetic determinants of "innate" T lymphocytes development and homeostasis

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Project Summary Innate conventional their requirement namely, molecules, the uncertain. systems, polymorphism mapping resources development a variation using T cells are a heterogeneous group of αβ and γδ T cells that respond much more r apidly than T cells upon activation. This swiftness of response r eflects their acquisition of functionality during development in the thymus. These innate T cells also share a non-MHC class I or II restriction for antigen recognition. Three major populations within the innate T cell group are recognized, the invariant NKT cells that recognize glycolipid antigens presented by non-polymorphic CD1d the mucosal associated invariant T (MAIT) cells t hat recognize vitamin metabolites presented by non-polymorphic MR1 molecules, and the gamma delta T cells which antigen specificities remain Altogether, these innate T cells, acting as bridges between the innate and adaptive immune contribute greatly to immune regulation and host protection. To appreciate the role that host play in steady-state evelopment and homeostasis of innate T cells, we propose to use QTL in the Collaborative Cross and Diversity Outbred (DO) mice. These genetically diverse mouse provide powerful experimental systems to test the ypothesis that variation in innate T cell and homeostasis is genetically regulated and to map the source of the diversity. We will conduct comprehensive screen of CC and DO strains for innate T cells to estimate the diversity resulting from genetic (Aim 1). We will then identify genes that underlie variation in innate T cell development/homeostasis QTL mapping (Aim 2). d h Given their capacity to link key inflammatory axes of innate and adaptive immunity, a better understanding of the molecular basis underpinning innate T cell development and plasticity, and how much this feature accounts for their pathophysiological roles, is critical for developing novel therapeutic approaches.