Mucosal-associated invariant T (MAIT) cells are numerous in humans and are implicated in various pathological settings. As such, understanding their biology is essential, and will lead to innovative therapeutic strategies. MAIT cells are selected on double positive thymocytes leading to memory phenotype and immediate effector functions. This original selection process targets MAIT cells to mucosal tissues in which they establish long term residency. MAIT cells are also found in secondary lymphoid organs, possibly providing B and T cell help during immune responses. Recent data suggest that MAIT cells migrate between mucosal tissues and their draining lymph nodes (LNs) at steady state and following inflammation. However, the role and dynamics of MAIT cells in LNs remain poorly understood. A comprehensive phenotypic and functional characterization of MAIT cells in various LNs and the corresponding organs is needed to decipher the specific role of LN MAIT cells within immune responses. Assessing the mechanisms involved in cell pool establishment and exchange will also help characterizing MAIT cell biology. We hypothesize that MAIT cells circulate back and forth between tissues and draining LNs, hence being poised in LNs to tissue-specific immune responses. Following tissue inflammation, this migration may ensure both adaptation of the LN response and mobilization of MAIT cells for rapid effector function in the tissue. Here we will test these hypotheses by 1) characterizing MAIT cells in mesenteric, mediastinal and inguinal/brachial LNs and in the drained tissues; 2) analyzing MAIT cell dynamics between different LNs and tissues at steady state, including pool establishment and mechanisms of migration and retention in LNs; 3) assessing MAIT cell effector functions following various triggers in different LNs and trafficking during inflammation. Building on long term expertise, specifically developed animal models and tools, and state-of-the-art techniques, this project will characterize the dynamics and functions of LN MAIT cells, to provide a conceptual framework that could be broaden to other unconventional T cells and resident memory cells.