Lepore Marco, Kalinichenko Artem, Calogero Salvatore, Kumar Pavanish, Paleja Bhairav, Schmaler Mathias, Narang Vipin, Zolezzi Francesca, Poidinger Michael, Mori Lucia, De Libero Gennaro
Department of Biomedicine, University Hospital and University of Basel, Basel, Switzerland.
Singapore Immunology Network, A*STAR, Singapore, Singapore.
Elife. 2017 May 18;6:e24476. doi: 10.7554/eLife.24476.
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.
主要组织相容性复合体I类相关分子MR1将与核黄素和叶酸相关的代谢产物呈递给黏膜相关恒定T细胞，但尚不清楚MR1是否能将其他抗原呈递给其他T细胞谱系。在健康个体中，我们鉴定出了受MR1限制的T细胞（命名为MR1T细胞），这些细胞表现出多样的TCR，并在没有微生物配体的情况下对表达MR1的细胞产生反应。对MR1T细胞克隆的分析揭示了其对不同细胞衍生抗原的特异性，以及抗原刺激后代谢编程、细胞周期控制和功能极化的替代转录策略。MR1T细胞克隆的表型和功能特征显示出多种趋化因子受体表达谱和多种效应分子的分泌，表明其功能具有异质性。因此，MR1T细胞在依赖MR1识别表达生理水平表面MR1的靶细胞时，表现出不同的辅助性T细胞样能力。这些数据扩展了MR1在微生物抗原呈递之外的作用，并表明MR1T细胞是人类T细胞库的正常组成部分。
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