Human MR1-restricted thymocytes share features of innate and adaptive T cells — ASN Events

Human MR1-restricted thymocytes share features of innate and adaptive T cells (#29)

Marielle Gold 1 , I Kurtz 1 , S Smyk Pearson 1
  1. OHSU/PVAMC, Portland, OREGON, United States

Human mucosal-associated invariant T (MAIT) cells predominantly express the semi-invariant T cell receptor TRAV1-2 and are restricted by the HLA-Ib molecule MR1. While MAIT cells share similarities with other innate T cells the extent to which MAIT cells are innate and their capacity to adapt is unknown. We evaluated the function of TRAV1-2+ T cells from the thymus, cord blood, and peripheral blood. While antigen-inexperienced MAIT cells displayed a naive phenotype these had intrinsic effector capacity in response to Mycobacterium tuberculosis (Mtb)-infected cells. TRAV1-2+ effector thymocytes contained sjTREC suggesting limited replication and thymic origin. In evaluating the capacity of Mtb-reactive MAIT cells to adapt, we found that those from peripheral blood demonstrated a memory phenotype and had undergone substantial expansion suggesting they responded to antigenic stimulation. Similarly to other non-classically restricted T cells with thymic function, MAIT cells in mice have been shown to be selected on a hematopoietic cell. In the human thymus we found that MR1 was uniquely and highly expressed on a subset of immature T cells. These cells display a number of distinctive features consistent with the possibility these cells may serve as antigen presenting cells to select human MAIT cells. MAIT cells, an evolutionarily conserved T cell subset that detects a variety of microbes, share features of innate and adaptive T cells.