TY - JOUR TI - Functionally diverse human T cells recognize non-microbial antigens presented by MR1 AU - Lepore, Marco AU - Kalinichenko, Artem AU - Calogero, Salvatore AU - Kumar, Pavanish AU - Paleja, Bhairav AU - Schmaler, Mathias AU - Narang, Vipin AU - Zolezzi, Francesca AU - Poidinger, Michael AU - Mori, Lucia AU - De Libero, Gennaro A2 - Yokoyama, Wayne M VL - 6 PY - 2017 DA - 2017/05/18 SP - e24476 C1 - eLife 2017;6:e24476 DO - 10.7554/eLife.24476 UR - https://doi.org/10.7554/eLife.24476 AB - MHC class I-related molecule MR1 presents riboflavin- and folate-related metabolites to mucosal-associated invariant T cells, but it is unknown whether MR1 can present alternative antigens to other T cell lineages. In healthy individuals we identified MR1-restricted T cells (named MR1T cells) displaying diverse TCRs and reacting to MR1-expressing cells in the absence of microbial ligands. Analysis of MR1T cell clones revealed specificity for distinct cell-derived antigens and alternative transcriptional strategies for metabolic programming, cell cycle control and functional polarization following antigen stimulation. Phenotypic and functional characterization of MR1T cell clones showed multiple chemokine receptor expression profiles and secretion of diverse effector molecules, suggesting functional heterogeneity. Accordingly, MR1T cells exhibited distinct T helper-like capacities upon MR1-dependent recognition of target cells expressing physiological levels of surface MR1. These data extend the role of MR1 beyond microbial antigen presentation and indicate MR1T cells are a normal part of the human T cell repertoire. KW - MR1 KW - T cell KW - antigen recognition JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -