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Journal articles on the topic 'Mucosal Associated Invariant T cell'

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Author: Grafiati

Published: 9 March 2023

Last updated: 10 March 2023

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1

Ghesquière, Thibault, Marion Ciudad, André Ramon, Hélène Greigert, Claire Gerard, Claudie Cladière, Marine Thébault, et al. "Mucosal-associated invariant T cells in Giant Cell Arteritis." Journal of Autoimmunity 121 (July 2021): 102652. http://dx.doi.org/10.1016/j.jaut.2021.102652.

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2

Koay, Hui-Fern, Dale I. Godfrey, and Daniel G. Pellicci. "Development of mucosal-associated invariant T cells." Immunology and Cell Biology 96, no. 6 (April 24, 2018): 598–606. http://dx.doi.org/10.1111/imcb.12039.

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3

Zhang, Yujue, Derun Kong, and Hua Wang. "Mucosal-Associated Invariant T cell in liver diseases." International Journal of Biological Sciences 16, no. 3 (2020): 460–70. http://dx.doi.org/10.7150/ijbs.39016.

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4

Jensen, Owen, Shubhanshi Trivedi, Jeremy D. Meier, and Daniel T. Leung. "Defining the role of mucosal-associated invariant T (MAIT) cells in B cell help." Journal of Immunology 204, no. 1_Supplement (May 1, 2020): 71.10. http://dx.doi.org/10.4049/jimmunol.204.supp.71.10.

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Abstract Pathogen-associated diarrheal diseases account for over 1.6 million deaths annually, yet the number of effective mucosal vaccines remains limited. An exciting potential target for mucosal vaccine adjuvants are mucosal-associated invariant T (MAIT) cells. MAITs are innate-like T cells which are found in the mucosa, blood, and secondary lymphoid organs (SLO), and can respond rapidly to conserved microbial antigens through cytokine secretion and cytotoxic effects. Recent evidence supports a role for MAITs in B cell help. We aim to improve mucosal vaccines by investigating a novel subset of T follicular helper (Tfh)-like MAIT cells and their ability to aid in B cell help and antibody mediated immunity. We describe Tfh-like MAITs from human blood and tonsil samples using linked TCR and phenotype single cell RNAseq, and in vitro culture assays. We further investigate the sufficiency of MAITs aid in antibody mediated immunity in vivo using a MAIT adoptive transfer model into Tcratm1Mom/J (αβ T cell deficient) mice followed by mucosal bacterial challenge. We identify a subset of CXCR5+ MAITs, enriched in human tonsils and murine SLOs that express the Tfh lineage defining transcription factor, BCL6, co-stimulatory markers and cytokines including IL-10 and IL-21 and can aid in B cell help in vitro. Likewise, in vivo we find that MAIT transfer induces pathogen-specific IgA but not IgG responses following mucosal challenge. Overall our study uncovered a novel subset of Tfh-like MAITs and has demonstrated the capacity of MAITs to provide help in antibody responses. Current work aims to uncover the mechanism of MAIT-B cell help which could critically inform efforts to target this population as mucosal adjuvants.

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5

Chua, Wei‐Jen, and Ted H. Hansen. "Bacteria, mucosal‐associated invariant T cells and MR1." Immunology & Cell Biology 88, no. 8 (August 24, 2010): 767–69. http://dx.doi.org/10.1038/icb.2010.104.

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6

Treiner, Emmanuel, Livine Duban, Ivan Cruz Moura, Ted Hansen, Susan Gilfillan, and Olivier Lantz. "Mucosal-associated invariant T (MAIT) cells: an evolutionarily conserved T cell subset." Microbes and Infection 7, no. 3 (March 2005): 552–59. http://dx.doi.org/10.1016/j.micinf.2004.12.013.

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7

Toubal, Amine, Isabelle Nel, Sophie Lotersztajn, and Agnès Lehuen. "Mucosal-associated invariant T cells and disease." Nature Reviews Immunology 19, no. 10 (July 15, 2019): 643–57. http://dx.doi.org/10.1038/s41577-019-0191-y.

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8

Ben Youssef, Ghada, Marie Tourret, Marion Salou, Liana Ghazarian, Véronique Houdouin, Stanislas Mondot, Yvonne Mburu, et al. "Ontogeny of human mucosal-associated invariant T cells and related T cell subsets." Journal of Experimental Medicine 215, no. 2 (January 16, 2018): 459–79. http://dx.doi.org/10.1084/jem.20171739.

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Mucosal-associated invariant T (MAIT) cells are semi-invariant Vα7.2+ CD161highCD4− T cells that recognize microbial riboflavin precursor derivatives such as 5-OP-RU presented by MR1. Human MAIT cells are abundant in adult blood, but there are very few in cord blood. We longitudinally studied Vα7.2+ CD161high T cell and related subset levels in infancy and after cord blood transplantation. We show that Vα7.2+ and Vα7.2− CD161high T cells are generated early during gestation and likely share a common prenatal developmental program. Among cord blood Vα7.2+ CD161high T cells, the minority recognizing MR1:5-OP-RU display a TRAV/TRBV repertoire very similar to adult MAIT cells. Within a few weeks of life, only the MR1:5-OP-RU reactive Vα7.2+ CD161high T cells acquire a memory phenotype. Only these cells expand to form the adult MAIT pool, diluting out other Vα7.2+ CD161high and Vα7.2− CD161high populations, in a process requiring at least 6 years to reach adult levels. Thus, the high clonal size of adult MAIT cells is antigen-driven and likely due to the fine specificity of the TCRαβ chains recognizing MR1-restricted microbial antigens.

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9

Cho, Young-Nan, Seung-Jung Kee, Tae-Jong Kim, Hye Mi Jin, Moon-Ju Kim, Hyun-Ju Jung, Ki-Jeong Park, et al. "Mucosal-Associated Invariant T Cell Deficiency in Systemic Lupus Erythematosus." Journal of Immunology 193, no. 8 (September 15, 2014): 3891–901. http://dx.doi.org/10.4049/jimmunol.1302701.

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10

Mak, Jeffrey Y. W., Ligong Liu, and David P. Fairlie. "Chemical Modulators of Mucosal Associated Invariant T Cells." Accounts of Chemical Research 54, no. 17 (August 20, 2021): 3462–75. http://dx.doi.org/10.1021/acs.accounts.1c00359.

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11

Le Bourhis, Lionel, Emmanuel Martin, Isabelle Péguillet, Amélie Guihot, Nathalie Froux, Maxime Coré, Eva Lévy, et al. "Antimicrobial activity of mucosal-associated invariant T cells." Nature Immunology 11, no. 8 (June 27, 2010): 701–8. http://dx.doi.org/10.1038/ni.1890.

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12

Torre, Pietro, Annalisa Brescia, Giorgio Giurato, Raffaella D’Auria, Francesca Rizzo, Benedetta Maria Motta, Valentina Giudice, et al. "Mucosal-Associated Invariant T Cells in T-Cell Non-Hodgkin Lymphomas: A Case Series." Cancers 14, no. 12 (June 14, 2022): 2921. http://dx.doi.org/10.3390/cancers14122921.

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Background: Mucosal-associated invariant T (MAIT) cells are a subset of unconventional T lymphocytes expressing a semi-invariant α/β T-cell receptor (TCR). The physiological functions of these cells, which are particularly abundant in normal liver and mucosal sites, have become clear only in recent years, but their role in most human diseases is still unknown. Since the cellular origin and etiopathogenesis of most T-lymphomas are still elusive, we decided to explore the presence of MAIT cells in biopsies from these neoplasms. Methods: Sixteen biopsies obtained from patients with a T-cell lymphoma diagnosis were analyzed via immunofluorescence staining using an anti-Vα7.2 antibody and the MR1-antigen tetramer. Positive cases were subjected to a polymerase chain reaction for the detection of Vα7.2–Jα33, Vα7.2–Jα20, or Vα7.2–Jα12 rearrangements, followed by sequencing of the CDR3α region. Results: CD3+/Vα7.2+ and CD3+/MR1-Ag-tetramer+ cells were found in 4 of 16 samples analyzed. The identification of specific TCR rearrangements confirmed the presence of these cells in all four samples. PCR and sequencing results documented the presence of multiple clones of MAIT cells in each positive sample. Conclusions: MAIT cells are frequently found in T-cell lymphomas. More in-depth studies and a larger number of samples are needed to better clarify the contribution of MAIT cells to this rare neoplasm.

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13

Berkson, Julia D., Chloe Slicter, Mukta Dutta, Haley Oberbillig, and Martin Prlic. "Title: Human mucosal-associated invariant T (MAIT) cells in inflamed tissues." Journal of Immunology 198, no. 1_Supplement (May 1, 2017): 200.1. http://dx.doi.org/10.4049/jimmunol.198.supp.200.1.

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Abstract Mucosal-associated invariant T (MAIT) cells recognize bacterial metabolites via a semi-invariant T cell receptor (TCR) presented by MHC-like molecule MR1. Once activated, MAIT cells are a potent effector population with cytotoxic and pro-inflammatory properties. We recently reported that a TCR signal is not sufficient to elicit effector function, instead pro-inflammatory cytokines in addition to a TCR signal are required for sustained MAIT cell effector functions. We proposed that this requirement allows MAIT cells to distinguish between commensal (TCR signal only) and pathogenic bacteria (TCR signal + inflammation). We next wanted to address how MAIT cells function within an inflamed tissue environment. Specifically, if inflammation resulted in increased MAIT effector function or an exhausted phenotype because of the sustained stimuli. We obtained gingival tissue and matched blood from donors undergoing periodontic surgery for various inflammation-related diseases. MAIT cells within inflamed mucosa showed increased effector function directly ex vivo compared to blood including expression of granzyme B and TNFa. RNAseq analysis of MAIT cells from inflamed mucosal tissue revealed a distinct transcriptional signature compared to MAIT cells in the blood. We observed a significant upregulation of chemotaxis and activation genes as well as inhibitory genes from multiple immune-modulatory pathways. Our data suggest that MAIT cells in inflamed tissues can maintain effector function, but also express immunomodulatory genes that presumably serve to avoid unwanted tissue damage.

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14

Held, Kathrin, Latika Bhonsle, Wakiro Sato, Geraldine Rühl, David Axel Laplaud, Reinhard Hohlfeld, and Klaus Dornmair. "T cell receptors of “mucosal-associated invariant T” cells in multiple sclerosis brain lesions." Journal of Neuroimmunology 275, no. 1-2 (October 2014): 200. http://dx.doi.org/10.1016/j.jneuroim.2014.08.536.

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15

Constantinides, Michael G., Jonathan L. Linehan, Shurjo Sen, Jahangheer Shaik, Sobhan Roy, Jess L. LeGrand, Nicolas Bouladoux, Erin J. Adams, and Yasmine Belkaid. "Mucosal-associated invariant T cells respond to cutaneous microbiota." Journal of Immunology 198, no. 1_Supplement (May 1, 2017): 218.15. http://dx.doi.org/10.4049/jimmunol.198.supp.218.15.

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Abstract The microbiome consists of a diverse array of commensal microorganisms that reside at barrier sites of the body and promote immune homeostasis through the release of microbial products, including derivatives of vitamin synthesis. Mucosal-associated invariant T (MAIT) cells are unconventional T cells that recognize vitamin B2 (riboflavin) derivatives presented by the major histocompatibility class I-like molecule, MR1. MAIT cells are predominantly located in barrier tissues, where they represent a substantial population of non-classical T cells and provide an initial defense to pathogens through their rapid production of either IL-17A or IFNg. However, it remains to be determined whether commensals regulate the development and function of MAIT cells. Here we show that MAIT cells are present in murine skin at a high frequency and their homeostasis requires the microbiota, as these lymphocytes are nearly absent in germ-free animals. Furthermore, application of distinct human commensal bacteria to the skin of mice induces the proliferation of IL-17A-producing MAIT cells that exhibit a unique transcriptional profile. The induction of these cells occurs in a manner that is partially dependent on both antigen presentation and IL-23 signaling. Additionally, MAIT cells stimulated by the cutaneous microbiota provide heterologous protection against subsequent pathogenic challenges. This work identifies MAIT cells as the only cell population that is entirely dependent on the microbiota and reveals the mechanism by which these cells respond to the commensal microbial community. Due to the high frequency of MAIT cells in human skin, these observations suggest that modulation of the skin-resident bacteria may have clinical applications.

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16

Bianchini, Elena, Sara De Biasi, Anna Maria Simone, Diana Ferraro, Patrizia Sola, Andrea Cossarizza, and Marcello Pinti. "Invariant natural killer T cells and mucosal-associated invariant T cells in multiple sclerosis." Immunology Letters 183 (March 2017): 1–7. http://dx.doi.org/10.1016/j.imlet.2017.01.009.

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17

Cassius, Charles, Mylene Branchtein, Maxime Battistella, Reyhan Amode, Clémence Lepelletier, Marie Jachiet, Adèle de Masson, et al. "Persistent deficiency of mucosal-associated invariant T cells during dermatomyositis." Rheumatology 59, no. 9 (December 17, 2019): 2282–86. http://dx.doi.org/10.1093/rheumatology/kez564.

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Abstract Objectives Mucosal-associated invariant T (MAIT) cells are innate-like lymphocytes that are important for antibacterial immunity and may have regulatory roles. MAIT cells are decreased during SLE. However, their frequencies and phenotype have not been investigated in DM. We studied MAIT cell frequencies and phenotype in DM patients with active and inactive disease (after treatment). Methods Peripheral blood flow cytometry analysis of MAIT cells was compared between DM (n = 22), SLE (n = 10), psoriasis (n = 7) and atopic dermatitis (n = 5) patients, and healthy controls (n = 19). Results A dramatic decrease of circulating MAIT cell frequency was observed in active DM and SLE patients compared with healthy controls and other inflammatory skin diseases [active DM: median = 0.25% (interquartile range 0.19–0.6%), P < 0.0001; active SLE: median = 0.61 (0.55–0.77), P < 0.0001 vs healthy controls: 2.32% (1.18–4.45%)]. MAIT cells from active DM patients had an abnormal phenotype including increased expression of CD25 and cytotoxic T-lymphocyte-associated protein 4 that correlated with their low frequency in the blood. Conclusion In DM, peripheral blood MAIT cells are dramatically reduced and have an activated/exhausted phenotype that may be linked to increased activation-induced cell death.

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18

Kwon, Yong Soo, Hye-Mi Jin, Young-Nan Cho, Moon-Ju Kim, Jeong-Hwa Kang, Hyun-Ju Jung, Ki-Jeong Park, Hae Jin Kee, Seung-Jung Kee, and Yong-Wook Park. "Mucosal-Associated Invariant T Cell Deficiency in Chronic Obstructive Pulmonary Disease." COPD: Journal of Chronic Obstructive Pulmonary Disease 13, no. 2 (November 9, 2015): 196–202. http://dx.doi.org/10.3109/15412555.2015.1069806.

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19

Sobkowiak, Michal, Haleh Davanian, Annelie Tjernlund, Anna Gibbs, Sushrusha Nayak, Edwin Leeansyah, Joana Dias, et al. "MAIT cells in the human oral mucosa are activated and perforinlow." Journal of Immunology 198, no. 1_Supplement (May 1, 2017): 149.8. http://dx.doi.org/10.4049/jimmunol.198.supp.149.8.

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Abstract Mucosa-associated invariant T (MAIT) cells are a class of non-classical T lymphocytes defined by their invariant Vα7.2-containing MR1-restricted T cell receptor, as well as high expression of CD161. At present, the characteristics of MAIT cells in the oral mucosa are poorly defined. In this study, we have analyzed buccal biopsies and matched blood samples from a cohort of healthy volunteers. MAIT cells were present in the buccal mucosa, with a tendency to cluster around the basal layer, a region also found to contain a higher frequency of MR1-expressing antigen-presenting cells. The frequency of MAIT cells was similar in the buccal mucosa compared to matched peripheral blood, in contrast to other major T cell subsets. However, the buccal mucosal MAIT cells displayed a tissue resident activated profile, with high CD69, HLA-DR and PD-1 expression, as well as a skewed subset distribution with higher representation of CD4/CD8 double-negative cells and of CD8αα+ cells within the CD8+ subset. The Jα chain usage in the MAIT cell TCR was more variable in oral mucosal MAIT cells than in peripheral blood MAIT cells. Functionally, the oral mucosal MAIT cells had lower perforin levels, indicative of a lower cytolytic potential. Interestingly, aspects of the oral MAIT cell population were associated with life-style factors such as consumption of bacterially fermented milk products and alcohol intake. Together, these data show that MAIT cells form a part of the oral mucosal T cell compartment, where they exhibit a tissue-resident activated profile. Thus, MAIT cells are positioned in the oral cavity and equipped to handle resident microbiota as well as invading pathogens.

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20

Legoux, François, Déborah Bellet, Celine Daviaud, Yara El Morr, Aurelie Darbois, Kristina Niort, Emanuele Procopio, et al. "Microbial metabolites control the thymic development of mucosal-associated invariant T cells." Science 366, no. 6464 (August 29, 2019): 494–99. http://dx.doi.org/10.1126/science.aaw2719.

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How the microbiota modulate immune functions remains poorly understood. Mucosal-associated invariant T (MAIT) cells are implicated in mucosal homeostasis and absent in germ-free mice. Here, we show that commensal bacteria govern murine MAIT intrathymic development, as MAIT cells did not recirculate to the thymus. MAIT development required RibD expression in bacteria, indicating that production of the MAIT antigen 5-(2-oxopropylideneamino)-6-d-ribitylaminouracil (5-OP-RU) was necessary. 5-OP-RU rapidly traveled from mucosal surfaces to the thymus, where it was captured by the major histocompatibility complex class Ib molecule MR1. This led to increased numbers of the earliest MAIT precursors and the expansion of more mature receptor-related, orphan receptor γt–positive MAIT cells. Thus, a microbiota-derived metabolite controls the development of mucosally targeted T cells in a process blurring the distinction between exogenous antigens and self-antigens.

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21

Reantragoon, Rangsima, Alexandra J. Corbett, Isaac G. Sakala, Nicholas A. Gherardin, John B. Furness, Zhenjun Chen, Sidonia B. G. Eckle, et al. "Antigen-loaded MR1 tetramers define T cell receptor heterogeneity in mucosal-associated invariant T cells." Journal of Experimental Medicine 210, no. 11 (October 7, 2013): 2305–20. http://dx.doi.org/10.1084/jem.20130958.

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Mucosal-associated invariant T cells (MAIT cells) express a semi-invariant T cell receptor (TCR) α-chain, TRAV1-2–TRAJ33, and are activated by vitamin B metabolites bound by the major histocompatibility complex (MHC)–related class I–like molecule, MR1. Understanding MAIT cell biology has been restrained by the lack of reagents to specifically identify and characterize these cells. Furthermore, the use of surrogate markers may misrepresent the MAIT cell population. We show that modified human MR1 tetramers loaded with the potent MAIT cell ligand, reduced 6-hydroxymethyl-8-d-ribityllumazine (rRL-6-CH2OH), specifically detect all human MAIT cells. Tetramer+ MAIT subsets were predominantly CD8+ or CD4−CD8−, although a small subset of CD4+ MAIT cells was also detected. Notably, most human CD8+ MAIT cells were CD8α+CD8β−/lo, implying predominant expression of CD8αα homodimers. Tetramer-sorted MAIT cells displayed a TH1 cytokine phenotype upon antigen-specific activation. Similarly, mouse MR1–rRL-6-CH2OH tetramers detected CD4+, CD4−CD8− and CD8+ MAIT cells in Vα19 transgenic mice. Both human and mouse MAIT cells expressed a broad TCR-β repertoire, and although the majority of human MAIT cells expressed TRAV1-2–TRAJ33, some expressed TRAJ12 or TRAJ20 genes in conjunction with TRAV1-2. Accordingly, MR1 tetramers allow precise phenotypic characterization of human and mouse MAIT cells and revealed unanticipated TCR heterogeneity in this population.

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22

Eckle, Sidonia B. G., Richard W. Birkinshaw, Lyudmila Kostenko, Alexandra J. Corbett, Hamish E. G. McWilliam, Rangsima Reantragoon, Zhenjun Chen, et al. "A molecular basis underpinning the T cell receptor heterogeneity of mucosal-associated invariant T cells." Journal of Experimental Medicine 211, no. 8 (July 21, 2014): 1585–600. http://dx.doi.org/10.1084/jem.20140484.

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Mucosal-associated invariant T (MAIT) cells express an invariant T cell receptor (TCR) α-chain (TRAV1-2 joined to TRAJ33, TRAJ20, or TRAJ12 in humans), which pairs with an array of TCR β-chains. MAIT TCRs can bind folate- and riboflavin-based metabolites restricted by the major histocompatibility complex (MHC)-related class I−like molecule, MR1. However, the impact of MAIT TCR and MR1-ligand heterogeneity on MAIT cell biology is unclear. We show how a previously uncharacterized MR1 ligand, acetyl-6-formylpterin (Ac-6-FP), markedly stabilized MR1, potently up-regulated MR1 cell surface expression, and inhibited MAIT cell activation. These enhanced properties of Ac-6-FP were attributable to structural alterations in MR1 that subsequently affected MAIT TCR recognition via conformational changes within the complementarity-determining region (CDR) 3β loop. Analysis of seven TRBV6-1+ MAIT TCRs demonstrated how CDR3β hypervariability impacted on MAIT TCR recognition by altering TCR flexibility and contacts with MR1 and the Ag itself. Ternary structures of TRBV6-1, TRBV6-4, and TRBV20+ MAIT TCRs in complex with MR1 bound to a potent riboflavin-based antigen (Ag) showed how variations in TRBV gene usage exclusively impacted on MR1 contacts within a consensus MAIT TCR-MR1 footprint. Moreover, differential TRAJ gene usage was readily accommodated within a conserved MAIT TCR-MR1-Ag docking mode. Collectively, MAIT TCR heterogeneity can fine-tune MR1 recognition in an Ag-dependent manner, thereby modulating MAIT cell recognition.

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Gu, Min, Derrick R. Samuelson, Christopher M. Taylor, Patricia E. Molina, Meng Luo, Robert W. Siggins, Judd E. Shellito, and David A. Welsh. "Alcohol‐associated intestinal dysbiosis alters mucosal‐associated invariant T‐cell phenotype and function." Alcoholism: Clinical and Experimental Research 45, no. 5 (April 3, 2021): 934–47. http://dx.doi.org/10.1111/acer.14589.

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24

Bolte, Fabian, and Barbara Rehermann. "Mucosal-Associated Invariant T Cells in Chronic Inflammatory Liver Disease." Seminars in Liver Disease 38, no. 01 (February 2018): 060–65. http://dx.doi.org/10.1055/s-0037-1621709.

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AbstractThe broadening field of microbiome research has led to a substantial reappraisal of the gut–liver axis and its role in chronic liver disease. The liver is a central immunologic organ that is continuously exposed to food and microbial-derived antigens from the gastrointestinal tract. Mucosal-associated invariant T (MAIT) cells are enriched in the human liver and can be activated by inflammatory cytokines and microbial antigens. In chronic inflammatory liver disease, MAIT cells are depleted suggesting an impaired MAIT cell-dependent protection against bacterial infections.

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25

Bennett, Michael S., Shubhanshi Trivedi, Anita S. Iyer, J. Scott Hale, and Daniel T. Leung. "Human mucosal-associated invariant T (MAIT) cells possess capacity for B cell help." Journal of Leukocyte Biology 102, no. 5 (August 14, 2017): 1261–69. http://dx.doi.org/10.1189/jlb.4a0317-116r.

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Seach, Natalie, Lucia Guerri, Lionel Le Bourhis, Yvonne Mburu, Yue Cui, Stéphanie Bessoles, Claire Soudais, and Olivier Lantz. "Double Positive Thymocytes Select Mucosal-Associated Invariant T Cells." Journal of Immunology 191, no. 12 (November 15, 2013): 6002–9. http://dx.doi.org/10.4049/jimmunol.1301212.

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27

Young, Mary H., and Laurent Gapin. "Mucosal associated invariant T cells: Don't forget your vitamins." Cell Research 23, no. 4 (December 4, 2012): 460–62. http://dx.doi.org/10.1038/cr.2012.168.

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Le Bourhis, Lionel, Emmanuel Martin, Isabelle Peguillet, Amélie Guihot, Maxime Coré, Mathilde Dusseaux, Vanessa Meyssonier, et al. "Anti-bacterial Function of Mucosal Associated Invariant T Cells." Clinical Immunology 135 (January 2010): S34—S35. http://dx.doi.org/10.1016/j.clim.2010.03.107.

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Ye, Longyun, Jiexue Pan, Muhammad Asghar Pasha, Xiaofei Shen, Shanti S. D’Souza, Ivan Ting Hin Fung, Yinna Wang, Bingnan Guo, Dale D. Tang, and Qi Yang. "Mucosal-associated invariant T cells restrict allergic airway inflammation." Journal of Allergy and Clinical Immunology 145, no. 5 (May 2020): 1469–73. http://dx.doi.org/10.1016/j.jaci.2019.12.891.

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Schneider, Marion, Rachel F. Hannaway, Rajesh Lamichhane, Sara M. Harpe, Joel D. A. Tyndall, Andrea J. Vernall, Anthony J. Kettle, and James E. Ussher. "Neutrophils suppress mucosal‐associated invariant T cells in humans." European Journal of Immunology 50, no. 5 (February 3, 2020): 643–55. http://dx.doi.org/10.1002/eji.201948394.

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31

Le Bourhis, Lionel, Lucia Guerri, Mathilde Dusseaux, Emmanuel Martin, Claire Soudais, and Olivier Lantz. "Mucosal-associated invariant T cells: unconventional development and function." Trends in Immunology 32, no. 5 (May 2011): 212–18. http://dx.doi.org/10.1016/j.it.2011.02.005.

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Kamiki, Jéssica, Patrícia António, Pedro Noronha, Carolina Condeço, Georgia Paraschoudi, Eric De Sousa, Andreia Maia, et al. "166 Mucosal-associated invariant T-cells (MAIT) in pancreatic cancer." Journal for ImmunoTherapy of Cancer 8, Suppl 3 (November 2020): A179. http://dx.doi.org/10.1136/jitc-2020-sitc2020.0166.

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BackgroundImmunotherapy has changed the standard of care for multiple cancers; however, its efficacy is limited. Chemotherapy and radiation had little effect in pancreatic ductal adenocarcinoma (PDAC) outcome1 in patients with metastatic disease, hence the urgency for new effective courses of treatment. Increasing evidence suggests mucosal-associated invariant T-cells (MAIT) play a role in anti-cancer T-cell responses, by recognizing transformed cells or bacterial products. MAIT respond towards microbial antigens and vitamin derivatives, produce pro-inflammatory cytokines2 3 and have been found present in primary and metastatic cancer lesions.3 4 Long-term survival PDAC patients present a unique microbiome pattern. In contrast, some microbial species may promote oncogenesis.5 6The focus of this project is the characterization of MAIT as immune effector cells in PDAC specimens.MethodsWe performed a retrospective analysis of long-term survivors (LTS) and short-term survivors (STS) patients with pancreatic cancer associating clinical endpoints with the presence of MAIT infiltration in the tumor tissue using immunofluorescence staining for MR1 (MHC class I-related gene, a MAIT ligand receptor), CD3 and TCR Vα7.2 (frequently reported chain in MAIT). Tumor infiltrating lymphocytes (TILs) were expanded and tested for recognition of microbial products presented to TILs or to PBMCs defined by cytokine production (ELISA), cytotoxicity (CD107a induction assay), CD69 or 4-1BB upregulation (flow cytometry). Reactive MAIT will be molecularly defined by deep TCR (T-cell receptor) sequencing which allows to ‘back-trace’ MR1 reactive TIL in the tumor specimen. The complex interaction of microbial antigen presentation from freshly harvested tumor specimens to TILs is being optimized for Nanolive technology that allows to follow live cell interactions for several days.ResultsTIL reactivity directed against microbial products from different bacterial species was detected by IFN-γ production and CD69 upregulation in responder TILs. A broader panel of TILs is currently being tested against bacterial species. TCRs will undergo laser microdissection for subsequent TCR repertoire sequencing. A more pronounced MAIT infiltration in close vicinity to tumor cells in LTS compared to STS is being studied, further supporting the anti-tumor role of MAIT.ConclusionsMAIT cells may exhibit anti-tumor properties, based on cytokine production and cellular marker activation. TCRs directed against cancer cells can serve as viable blueprints to engage with MR1 on PDAC recognizing tumor-associated targets or microbial products that elicit IFN-γ production. This allows to explore MAIT TCRs for adoptive therapies or distinct microbial species that drive clinically relevant responses.AcknowledgementsThe authors would like to thank to Champalimaud Foundation Biobank and Vivarium Facility at Champalimaud Foundation.Ethics ApprovalThis study was approved by the Champalimaud Foundation Ethics Committee and by Ethics Research Committee of NOVA Medical School of NOVA University of Lisbon.ConsentFor each patient, written informed consent and approval by the Ethical Committee of the Champalimaud Foundation will be obtained. The study will be in compliance with the Declaration of Helsinki.ReferencesSideras, K. et al. Role of the immune system in pancreatic cancer progression and immune modulating treatment strategies. Cancer Treat. Rev 2014;40: 513–522.Toubal A, Nel I, Lotersztajn S & Lehuen A. Mucosal-associated invariant T cells and disease. Nat Rev. Immunol 2019;19:643–657.Lukasik Z, Elewaut D & Venken K. Mait cells come to the rescue in cancer immunotherapy?Cancers (Basel). 12, 1–19 ( 2020).Vacchini A, Chancellor A., Spagnuolo J., Mori L. & De Libero G. MR1-restricted t cells are unprecedented cancer fighters. Front Immunol 2020;11:1–8.Aykut B, et al. The fungal mycobiome promotes pancreatic oncogenesis via activation of MBL. Nature 2019:574;264–267.Pushalkar S, et al. The pancreatic cancer microbiome promotes oncogenesis by induction of innate and adaptive immune suppression. Cancer Discov 2018;8:403–416.

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Hayashi, Eri, Asako Chiba, Kurisu Tada, Keiichi Haga, Mie Kitagaichi, Shihoko Nakajima, Makio Kusaoi, et al. "Involvement of Mucosal-associated Invariant T cells in Ankylosing Spondylitis." Journal of Rheumatology 43, no. 9 (July 1, 2016): 1695–703. http://dx.doi.org/10.3899/jrheum.151133.

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Objective.Ankylosing spondylitis (AS) is characterized by chronic inflammation of the axial and peripheral joints and ligamentous attachments. Gut immunity is thought to be involved in AS, because a prominent coexistence of gut and joint inflammation has been observed in patients with AS. Mucosal-associated invariant T (MAIT) cells are preferentially located in the gut lamina propria and produce inflammatory cytokines such as interleukin 17 (IL-17) and tumor necrosis factor-α (TNF-α), which are therapeutic targets for AS. This study aimed to investigate the involvement of MAIT cells in AS.Methods.The frequency of MAIT cells and their cytokine production were determined in patients with AS and healthy controls (HC). The expression of a MAIT cell activation marker (CD69) was analyzed in patients with AS by using flow cytometry.Results.The frequency of MAIT cells in the peripheral blood was lower in patients with AS compared with HC. The levels of IL-17 produced by MAIT cells after activation were higher in patients with AS than in the HC. CD69 expression on MAIT cells correlated with the Ankylosing Spondylitis Disease Activity Score in patients with AS.Conclusion.These results suggest the involvement of MAIT cells in the pathogenesis of AS.

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DeAngelis, Lara Marie, Nicola Cirillo, Alexis Perez-Gonzalez, and Michael McCullough. "Characterization of Mucosal-Associated Invariant T Cells in Oral Lichen Planus." International Journal of Molecular Sciences 24, no. 2 (January 12, 2023): 1490. http://dx.doi.org/10.3390/ijms24021490.

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Oral lichen planus (OLP) is an inflammatory condition of unknown cause that has been associated with concurrent candidal infection. Mucosal-associated invariant T (MAIT) cells express the T cell receptor TCRVα7.2 and are activated by riboflavin intermediates produced by microbes. The interaction between MAIT cells, Candida, and OLP is unknown. This study aimed to determine mucosal-associated T cell presence in OLP and whether the abundance of these cells changed due to the presence of either Candida or symptoms, using multiplex immunohistochemistry (mIHC). Ninety formalin fixed-paraffin-embedded (FFPE) tissue samples were assessed using mIHC for the cellular markers CD3, interleukin 18 receptor one (IL18R1), TCRVα7.2, CD161, CD8, and major histocompatibility complex class I-related (MR-1) protein. The samples were stratified into five groups on the basis of clinical (presence/absence of symptoms) and microbiological (presence/absence of Candida) criteria. Results demonstrated the presence of MAIT cell phenotypes in OLP inflammatory infiltrate within the connective tissue. Significant differences existed between different OLP groups with the percentage of log(CD3+ CD161+) and log(CD3+ TCRVα7.2+) positive cells (p < 0.001 and p = 0.005 respectively). Significant differences also existed with the relative abundance of triple-stained log(CD3+ CD161+ IL18R1+) cells (p = 0.004). A reduction in log(CD3+ CD161+ IL18R1+) cells was observed in lesional tissue of patients with symptomatic OLP with and without Candida when compared to controls. When present in OLP, MAIT cells were identified within the connective tissue. This study demonstrates that mIHC can be used to identify MAIT cell phenotypes in OLP. Reduced percentage of log(CD3+ CD161+ IL18R1+) cells seen in symptomatic OLP with and without Candida suggests a role for these cells in OLP pathogenesis.

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Yu, Chen, Sejiro Littleton, Nicholas S. Giroux, Rose Mathew, Shengli Ding, Joan Kalnitsky, Yuchen Yang, et al. "Mucosal-associated invariant T cell responses differ by sex in COVID-19." Med 2, no. 6 (June 2021): 755–72. http://dx.doi.org/10.1016/j.medj.2021.04.008.

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Cui, Yue, Katarzyna Franciszkiewicz, Yvonne K. Mburu, Stanislas Mondot, Lionel Le Bourhis, Virginie Premel, Emmanuel Martin, et al. "Mucosal-associated invariant T cell–rich congenic mouse strain allows functional evaluation." Journal of Clinical Investigation 125, no. 11 (October 12, 2015): 4171–85. http://dx.doi.org/10.1172/jci82424.

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Gold, Marielle C., Stefania Cerri, Susan Smyk-Pearson, Meghan E. Cansler, Todd M. Vogt, Jacob Delepine, Ervina Winata, et al. "Human Mucosal Associated Invariant T Cells Detect Bacterially Infected Cells." PLoS Biology 8, no. 6 (June 29, 2010): e1000407. http://dx.doi.org/10.1371/journal.pbio.1000407.

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Huang, Shouxiong, Susan Gilfillan, Marina Cella, Michael J. Miley, Olivier Lantz, Lonnie Lybarger, Daved H. Fremont, and Ted H. Hansen. "Evidence for MR1 Antigen Presentation to Mucosal-associated Invariant T Cells." Journal of Biological Chemistry 280, no. 22 (March 31, 2005): 21183–93. http://dx.doi.org/10.1074/jbc.m501087200.

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Huang, Shouxiong, Susan Gilfillan, Sojung Kim, Bruce Thompson, Xiaoli Wang, Andrea J. Sant, Daved H. Fremont, Olivier Lantz, and Ted H. Hansen. "MR1 uses an endocytic pathway to activate mucosal-associated invariant T cells." Journal of Cell Biology 181, no. 3 (May 5, 2008): i11. http://dx.doi.org/10.1083/jcb1813oia11.

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Cassius, C., M. Branchtein, M. Battistella, C. Lepelletier, A. De Masson, A. Bensussan, M. Bagot, H. Le Buanec, and J. Bouaziz. "043 Persistent deficiency of mucosal associated invariant T cells in dermatomyositis." Journal of Investigative Dermatology 139, no. 9 (September 2019): S222. http://dx.doi.org/10.1016/j.jid.2019.07.046.

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Sugimoto, Chie, Hiroyoshi Fujita, and Hiroshi Wakao. "Harnessing the Power of Mucosal-Associated Invariant T (MAIT) Cells in Cancer Cell Therapy." Biomedicines 10, no. 12 (December 7, 2022): 3160. http://dx.doi.org/10.3390/biomedicines10123160.

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Mucosal-associated invariant T (MAIT) cells, a burgeoning type of the innate-like T cells, play a crucial role in maintaining immune homeostasis, particularly in host defense. Although many studies have implied the use of MAIT cells in tumor immunity, whether MAIT cells are pro-tumor or anti-tumor has remained elusive, as in the case for other innate-like T cells that possess dichotomous roles in tumor immunity. Although this difficulty persists where endogenous MAIT cells are the target for therapeutic intervention, the advent of induced pluripotent stem-cell-derived MAIT cells (reMAIT cells) will make it possible to harness these cells for immune cell therapy. In this review, we will discuss possible roles of MAIT cells in tumor immunity and the potential of reMAIT cells to treat tumors.

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Sa, Moa, Sojeong Kim, Won Kim, and Su-Hyung Park. "Characterizations of mucosal associated invariant T cells in alcoholic liver disease." Journal of Immunology 198, no. 1_Supplement (May 1, 2017): 65.12. http://dx.doi.org/10.4049/jimmunol.198.supp.65.12.

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Abstract The liver is a critical immunological site for chronic alcohol consumption as it filters various antigens activating both innate and adaptive responses. The pathogenesis of alcoholic liver disease (ALD) in human is not clear in terms of the specific role of immune cell population. Mucosal associated invariant T (MAIT) cells are found to be abundant in the mucosal organs, especially within the liver organ in which the cells comprise up to 50 % of T cells. Here, we show that the percentage of circulating MAIT cells is severely reduced in ALD patients (p=0.0028), including patients with steatohepatitis (ASH, n=20), steatohepatitis with cirrhosis (ASHAC, n=15) and cirrhosis (AC, n=12), compared to age-matched healthy donors (HD, n=8). Moreover, compared to non-liver disease group, MAIT cells are depleted among liver infiltrating lymphocytes in ASH (p=0.0276) and ASHAC (p=0.0049) patients, whereas that of AC group is recovered. Although the percentage of MAIT cells is decreased, the cells display increased expression level of activation markers. Pro-inflammatory cytokines such as IL-17A and MIP-1 beta are up-regulated in ASH and ASHAC patients by PMA/Ionomycin stimulation. In addition, Perforin and Granzyme B, which are cytotoxic markers in granule, are significantly increased in both peripheral blood and liver of ASHAC group. Taken together, our results suggest that activated MAIT cell population in the liver may contribute to the pathogenesis of ALD.

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Burman, Poromendro, Boyang Zhang, Zhicheng Ji, Justina Caushi, Frank Housseau, Andrew Pardoll, Zhang Jiajia, Hongkai Ji, and Kellie Smith. "286 Sex differences in the transcriptional profiles of mucosal-associated invariant T cells in neoadjuvant anti-PD-1 treated non-small cell lung cancer (NSCLC)." Journal for ImmunoTherapy of Cancer 9, Suppl 2 (November 2021): A310. http://dx.doi.org/10.1136/jitc-2021-sitc2021.286.

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BackgroundMucosal Associated Invariant T Cells (MAIT cells) are unconventional T cells that recognize vitamin B metabolites derived from bacteria and are mainly present in mucosal tissues and peripheral blood.1 Their activation by T Cell Receptor (TCR)-dependent and -independent pathways can result in effector function that can either promote or inhibit cytotoxic effects.2 MAIT cells are known to be involved in the pathogenesis of multiple diseases that involve mucosal tissues, such as non-small cell lung cancer (NSCLC).2 Recently, studies have shown that disparate outcomes to SARS-CoV-2-infection between males and females may involve a differential activation of MAIT cells in the lung mucosa.3 It is therefore conceivable to hypothesize that sex differences of MAIT cells in NSCLC may also impact outcome, however their involvement in progression and subsequent treatment response of NSCLC has never been explored.MethodsTo study the transcriptional program of MAIT cells in NSCLC as a function of sex, peripheral blood and tissue biospecimens were obtained from the first-in-human clinical trial of neoadjuvant anti-PD-1 (nivolumab) in resectable non-small cell lung cancer; NCT02259621.4 Coupled single-cell RNAseq/TCRseq was performed on tumor infiltrating lymphocytes (TIL), paired adjacent normal lung, and tumor-draining lymph nodes (TDLN). MAIT cells were identified by expression of SLC4A10 and the invariant TRAV1-2 and TRAJ33/12/20 TCR. Computational analysis revealed 4 distinct MAIT cell clusters and differentially expressed genes in the tumors and healthy normal lung of males as compared to females.ResultsIn MAIT cells from females, we found upregulation of CD8A, GNLY, and NKG7 genes. These genes are involved with T cell activation and cytolytic function, suggesting that the activation of these genes in MAIT cells could be contributing towards their cytolytic activity in females. In MAIT cells from males, we found upregulation of PDE3B and PCBP2 genes, which are known to be involved with immunosuppression and downregulation of cytotoxic T lymphocyte (CTL) responses. These findings were consistent in the healthy normal lung, suggesting these transcriptional programs may be due to the normal lung biology and not necessarily a byproduct of carcinogenesis.ConclusionsThese results highlight the potential for dual characteristics of MAIT cells in neoadjuvant anti-PD-1-treated NSCLCs and provide an important foundation in our study of the often dichotomous responses between males and females to immunotherapy. Future analyses will focus on the interplay of MAIT cells with other cells in the tumor microenvironment (TME) as a function of immunotherapy treatment and clinical response.ReferencesChen Z, Wang H, D’Souza C, et al. Mucosal-associated invariant T-cell activation and accumulation after in vivo infection depends on microbial riboflavin synthesis and co-stimulatory signals. Mucosal Immunol 2017;10:58–68.Wen X, Zhang X, et al. Title of article: mucosal-associated invariant T cells in lung cancers. Elsevier 2021;94.Yu C, Littleton S, et al. Mucosal-associated invariant T cell responses differ by sex in COVID-19. CellPress 2021;2:755–772.Caushi JX, Zhang J, Ji Z, et al. Transcriptional programs of neoantigen-specific TIL in anti-PD-1-treated lung cancers. Nature 2021.Ethics ApprovalThis study was approved by the Institutional Review Boards (IRB) at Johns Hopkins University (JHU) and Memorial Sloan Kettering Cancer Center and was conducted in accordance with the Declaration of Helsinki and the International Conference on Harmonization Good Clinical Practice guidelines. The patients described in this study provided written informed consent.

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Huang, Shouxiong, Susan Gilfillan, Sojung Kim, Bruce Thompson, Xiaoli Wang, Andrea J. Sant, Daved H. Fremont, Olivier Lantz, and Ted H. Hansen. "MR1 uses an endocytic pathway to activate mucosal-associated invariant T cells." Journal of Experimental Medicine 205, no. 5 (April 28, 2008): 1201–11. http://dx.doi.org/10.1084/jem.20072579.

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Like CD1d-restricted iNKT cells, mucosal-associated invariant T cells (MAITs) are “innate” T cells that express a canonical TCRα chain, have a memory phenotype, and rapidly secrete cytokines upon TCR ligation. Unlike iNKT cells, MAIT cells require the class Ib molecule MHC-related protein I (MR1), B cells, and gut flora for development and/or expansion, and they preferentially reside in the gut lamina propria. Evidence strongly suggests that MAIT cell activation is ligand-dependent, but the nature of MR1 ligand is unknown. In this study, we define a mechanism of endogenous antigen presentation by MR1 to MAIT cells. MAIT cell activation was dependent neither on a proteasome-processed ligand nor on the chaperoning by the MHC class I peptide loading complex. However, MAIT cell activation was enhanced by overexpression of MHC class II chaperones Ii and DM and was strikingly diminished by silencing endogenous Ii. Furthermore, inhibiting the acidification of the endocytic compartments reduced MR1 surface expression and ablated MAIT cell activation. The importance of the late endosome for MR1 antigen presentation was further corroborated by the localization of MR1 molecules in the multivesicular endosomes. These findings demonstrate that MR1 traffics through endocytic compartments, thereby allowing MAIT cells to sample both endocytosed and endogenous antigens.

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Sakala, Isaac, Lars Kjer-Nielsen, Christopher Eickhoff, Xiaoli Wang, Ligong Liu, David Fairlie, Jamie Rossjohn, Daniel Hoft, and Ted Hansen. "Tetramer identification of functional mouse mucosal associated invariant T cells (INC6P.352)." Journal of Immunology 192, no. 1_Supplement (May 1, 2014): 121.19. http://dx.doi.org/10.4049/jimmunol.192.supp.121.19.

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Abstract Mucosal associated invariant T (MAIT) cells have a semi-invariant TCR Vα chain, and their development is dependent upon the commensal flora and the expression of MR1. MAIT cells are activated in vitro in an MR1-restricted manner by cells infected with diverse strains of bacteria suggesting a widely shared antigen. Such an antigen was recently defined by the observation that human MR1 binds bacterial riboflavin metabolites (ribityllumazines, RL antigens) that are capable of activating MAIT cells. Recently MR1/RL tetramers were constructed allowing us to compare MR1-dependency and function of mouse MAIT cell subsets in invariant TCR Vα19-Jα33 (Vα19i) transgenic (Tg) mice. Although significant numbers of tetramer+ cells were detected in both MR1+/+ and MR1-/- Vα19i Tg mice, only tetramer+ cells from MR1+/+ and not MR1-/- Vα19i Tg mice had predominant expression of CD69, NK1.1 and Vβ6/8 and displayed robust in vitro responses to IL-12+IL-18 or RL Ag. In addition, tetramer+ MAIT cells expressing CD4, CD8 or neither developing in MR1+/+ Vα19i Tg mice had disparate cytokine profiles in response to RL Ag. Most notably, after mycobacterial infection all MAIT cell subsets decreased in the blood regardless of whether they express NK1.1 and/or Vβ6/8; however, only the NK1.1+Vβ6/8+ subset predominated in the lung airways of infected MR1+/+ Vα19i Tg mice. These findings present evidence for the functional diversity of MAIT cell responses to innate cytokines, RL Ag and bacterial infection.

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Bhattacharyya, Abir, Laïla-Aïcha Hanafi, Alyssa Sheih, Jonathan L. Golob, Sujatha Srinivasan, Michael J. Boeckh, Steven A. Pergam, et al. "Graft-Derived Reconstitution of Mucosal-Associated Invariant T Cells after Allogeneic Hematopoietic Cell Transplantation." Biology of Blood and Marrow Transplantation 24, no. 2 (February 2018): 242–51. http://dx.doi.org/10.1016/j.bbmt.2017.10.003.

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O’Neill, Chloe, Féaron C. Cassidy, Donal O’Shea, and Andrew E. Hogan. "Mucosal Associated Invariant T Cells in Cancer-Friend or Foe?" Cancers 13, no. 7 (March 30, 2021): 1582. http://dx.doi.org/10.3390/cancers13071582.

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Mucosal associated invariant T (MAIT) cells are a population of unconventional T cells which can bridge the innate and adaptive immune systems. Well-described roles for MAIT cells include host protection against invading bacteria, fungi and viruses. Upon activation, MAIT cells become prolific effector cells, capable of producing a range of cytokines and lytic molecules. In addition to their anti-microbial role, MAIT cells have been implicated in immune responses to cancer, with opposing beneficial and pathogenic roles reported. On the one hand, MAIT cells can home to the site of the tumour in many human cancers and can produce anti-tumour molecules. On the other, MAIT cells can display defective phenotypes in certain cancers and produce pro-tumour molecules. In this review, we discuss the current literature on the diverse roles for MAIT cells in cancer, outlining their frequencies, functions and associations with N staging and prognosis. We also discuss potential mechanisms underpinning cancer-related alterations in MAIT cells and highlight therapeutic approaches to harness or target MAIT cells in cancer.

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Le Bourhis, Lionel, Emmanuel Martin, Isabelle Péguillet, Amélie Guihot, Nathalie Froux, Maxime Coré, Eva Lévy, et al. "Erratum: Corrigendum: Antimicrobial activity of mucosal-associated invariant T cells." Nature Immunology 11, no. 10 (October 2010): 969. http://dx.doi.org/10.1038/ni1010-969a.

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Shigematsu, Hiroaki, Kenichi Kumagai, Motoaki Suzuki, Takanori Eguchi, Ryota Matsubara, Yasunari Nakasone, Keisuke Nasu, et al. "Cross-Reactivity of Palladium in a Murine Model of Metal-induced Allergic Contact Dermatitis." International Journal of Molecular Sciences 21, no. 11 (June 5, 2020): 4061. http://dx.doi.org/10.3390/ijms21114061.

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Metal allergy is usually diagnosed by patch testing, however, the results do not necessarily reflect the clinical symptoms because of cross-reactivity between different metals. In this study, we established the novel mouse model of cross-reactive metal allergy, and aimed to elucidate the immune response in terms of T-cell receptor repertoire. This model was classified into two groups: the sensitization to nickel and challenge with palladium group, and the sensitization to chromium and challenge with palladium group. This model developed spongiotic edema with intra- and peri-epithelial infiltration of CD4+ T cells in the inflamed skin that resembles human contact dermatitis. Using T cell receptor analysis, we detected a high proportion of T cells bearing Trav8d-1-Traj49 and Trav5-1-Traj37 in the Ni- and Cr-sensitized Pd-challenged mice. Furthermore, mucosal-associated invariant T cells and invariant natural killer T cells were also detected. Our results indicated that T cells bearing Trav8d-1-Traj49 and Trav5-1-Traj37 induced the development of palladium-cross reactive allergy, and that mucosal-associated invariant T and invariant natural killer T cells were also involved in the cross-reactivity between different metals.

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Flores-Villanueva, Pedro, Navid Sobhani, Xu Wang, and Yong Li. "MR1-Restricted T Cells in Cancer Immunotherapy." Cancers 12, no. 8 (August 3, 2020): 2145. http://dx.doi.org/10.3390/cancers12082145.

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Major histocompatibility complex class I-related (MR1) was first identified as a cell membrane protein involved in the development and expansion of a unique set of T cells expressing an invariant T-cell receptor (TCR) α-chain. These cells were initially discovered in mucosal tissues, such as the intestinal mucosa, so they are called mucosal-associated invariant T (MAIT) cells. MR1 senses the presence of intermediate metabolites of riboflavin and folic acid synthesis that have been chemically modified by the side-products of glycolysis, glyoxal or methylglyoxal. These modified metabolites form complexes with MR1 and translocate from the endoplasmic reticulum to the plasma membrane where MAIT cells’ TCRs recognize them. Recent publications report that atypical MR1-restricted cytotoxic T cells, differing from MAIT cells in TCR usage, antigen, and transcription factor profile, recognize an as yet unknown cancer-specific metabolite presented by MR1 in cancer cells. This metabolite may represent another class of neoantigens, beyond the neo-peptides arising from altered tumor proteins. In an MR1-dependent manner, these MR1-restricted T cells, while sparing noncancerous cells, kill many cancer cell lines and attenuate cell-line-derived and patient-derived xenograft tumors. As MR1 is monomorphic and expressed in a wide range of cancer tissues, these findings raise the possibility of universal pan-cancer immunotherapies that are dependent on cancer metabolites.

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