Journal Article

Functionally diverse human T cells recognize non-microbial antigens presented by MR1

Kumar, Pavanish, Lepore, Marco, Narang, Vipin, Poidinger, Michael, Schmaler, Mathias, Paleja, Bhairav, Kalinichenko, Artem, De Libero, Gennaro, Mori, Lucia, Calogero, Salvatore, Zolezzi, Francesca

2017

Overview

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. White blood cells called T cells recognize germs and infected cells, and get rid of other cells in the body that look different to healthy cells – for example, tumor cells. These activities all depend on a molecule called the T cell receptor (or TCR for short), which is found on the surface of the T cells. Each TCR interacts with a specific complex on the surface of the target cell. One of the molecules recognized by the TCR is known as MHC class I-related (shortened to MR1). This molecule attracts TCRs to infected cells, but it was not know if the MR1 molecule could attract TCRs to cancer cells too. Lepore et al. now show that there are indeed T cells in humans that recognize cancer cells through interaction with the MR1 molecules produced by the cancer cells. This new group of T cells has been named MR1T, and the cells can be easily detected in the blood of healthy individuals. The cells can be classified as a new cell population based on their capacity to recognize MR1 and how they react with different types of cancer cells. Importantly, the MR1 that attracts these TCRs is the same in all people, and so the same TCR may recognize MR1-expressing cancer cells from different patients. The next challenge is to identify MR1T cells that recognize and kill cancer cells from different tissues. These studies will hopefully pave the way for new and broader strategies to combat cancer.

• Publisher: eLife Science Publications, Ltd,eLife Sciences Publications Ltd,eLife Sciences Publications, Ltd
• Subject: Antigen Presentation / antigen recognition / Antigens / Antigens - immunology / Antigens - metabolism / Cell cycle / Cell Line / Cytokines / Cytokines - secretion / Folic acid / Gene expression / Health aspects / Histocompatibility Antigens Class I - metabolism / Humans / Immunology / Leukemia / Ligands / Lymphocytes / Lymphocytes T / Magnetic resonance imaging / Major histocompatibility complex / Metabolites / Methods / Minor Histocompatibility Antigens - metabolism / MR1 / Mucosa / Population / Proteins / Receptors, Chemokine - biosynthesis / Riboflavin / Software / T cell / T cell receptors / T cells / T-Lymphocytes - immunology / Transcription / Transcription factors