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

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

doi:10.7554/elife.29743

Cited by 17 publications

(14 citation statements)

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“…40 Furthermore, the TCR a-chain can feature diversity beyond the canonical TRAV1-2-TRAJ33 rearrangement, where frequently also TRAJ12 and 20 are used 4,5,61 but also other TRAJ segments including some that lack the Tyr 95 residue, 62 that was shown to be pivotal in MAIT cell activation, hydrogen bonding with the ribityl moiety of activating Ags. 4,5,28,39,40,42,61,63 Furthermore, diverse TRAV1-2 À TCRs with various reactivity patterns have been described: (i) some reacted like classical MAIT TCRs with MR1-5-OP-RU tetramers only 61 ; (ii) others reacted with both tetramers with folic acid-derived ligands and 5-OP-RU, 61 or in one case responded to both riboflavin pathway-derived Ags and a riboflavin-deficient microbe (S. pyogenes) 64 and as such overlapped with the classical MAIT cell reactivity; (iii) a third type reacted with tetramers with folic acid-derived ligands only 61 or responded to self-Ags only 65 and as such was not overlapping with the classical MR1-5-OP-RU-reactive T-cell subset. Gold et al 62 also observed distinct MAIT TCR repertoire mobilization in response to diverse pathogens that could reflect the existence of discrete pathogen-associated Ags presented by MR1.…”

Section: Reflections On Mr1 Antigen Diversitymentioning

confidence: 99%

“…The discovery of 5-OP-RU and 5-OE-RU as very potent Ags and the development of MR1-tetramers, 5,42 now available from the National Institutes of Health, USA, have opened up the field to start elucidating the roles of MAIT cells in anti-microbial immunity, 19,[66][67][68][69][70] in sensing of metabolic changes such as in cancer, stress and cell damage, 65,71 as well as in immunopathology. [72][73][74] The tetramers have also allowed further characterization of the phenotypic identity of MAIT cells and their development, with individual-and age-specific differences now being investigated.…”

Section: Where To Nextmentioning

confidence: 99%

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An overview on the identification of MAIT cell antigens

et al. 2018

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Mucosal associated invariant T (MAIT) cells are restricted by the monomorphic MHC class I-like molecule, MHC-related protein-1 (MR1). Until 2012, the origin of the MAIT cell antigens (Ags) was unknown, although it was established that MAIT cells could be activated by a broad range of bacteria and yeasts, possibly suggesting a conserved Ag. Using a combination of protein chemistry, mass spectrometry, cellular biology, structural biology and small molecule chemistry, we discovered MR1 ligands derived from folic acid (vitamin B9) and from an intermediate in the microbial biosynthesis of riboflavin (vitamin B2). While the folate derivative 6-formylpterin generally inhibited MAIT cell activation, two riboflavin pathway derivatives, 5-(2-oxopropylideneamino)-6-D-ribitylaminouracil and 5-(2-oxoethylideneamino)-6-D-ribitylaminouracil, were potent MAIT cell agonists. Other intermediates and derivatives of riboflavin synthesis displayed weak or no MAIT cell activation. Collectively, these studies revealed that in addition to peptide and lipid-based Ags, small molecule natural product metabolites are also ligands that can activate T cells expressing αβ T-cell receptors, and here we recount this discovery.

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Section: Reflections On Mr1 Antigen Diversitymentioning

confidence: 99%

Section: Where To Nextmentioning

confidence: 99%

An overview on the identification of MAIT cell antigens

et al. 2018

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“…Blood-derived MAIT cells respond to different antigens by distinct changes in the surface marker expression [107,141]. Further studies showed the existence of a broader MR1 ligand repertoire including ligands derived from riboflavin-auxotroph bacteria [56,67], mammalian cells [103] and drugs [92]. Some metabolites of folic acids such as 6-formylpterin (6-FP) and acetyl-6-FP as well as bacterial ligands do bind to MR1 but act as antagonists [45, 67,93] suggesting that the function is modulated depending on the specific antigen-MR1 interaction.…”

Section: Mucosal-associated Invariant T Cellsmentioning

confidence: 99%

Human unconventional T cells in Plasmodium falciparum infection

et al. 2020

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Malaria is an old scourge of humankind and has a large negative impact on the economic development of affected communities. Recent success in malaria control and reduction of mortality seems to have stalled emphasizing that our current intervention tools need to be complemented by malaria vaccines. Different populations of unconventional T cells such as mucosal-associated invariant T (MAIT) cells, invariant natural killer T (iNKT) cells and γδ T cells are gaining attention in the field of malaria immunology. Significant advances in our basic understanding of unconventional T cell biology in rodent malaria models have been made, however, their roles in humans during malaria are less clear. Unconventional T cells are abundant in skin, gut and liver tissues, and long-lasting expansions and functional alterations were observed upon malaria infection in malaria naïve and malaria pre-exposed volunteers. Here, we review the current understanding of involvement of unconventional T cells in anti-Plasmodium falciparum immunity and highlight potential future research avenues.

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“…MR1 is a non-polymorphic MHC class I–like molecule that presents small metabolites to T cells. In humans, the MR1-restricted T cell pool consists of two populations, mucosal-associated invariant T (MAIT) cells ( Porcelli et al, 1993 ; Treiner et al, 2003 ) and MR1T cells ( Harriff et al, 2018 ; Lepore et al, 2017 ), which significantly differ in antigen (Ag) specificity and TCR repertoire. While MR1T cells react to not yet identified self and potential tumor-associated Ags ( Harriff et al, 2018 ; Lepore et al, 2017 ) and display polyclonal TCRs, MAIT cells recognize microbial metabolites and are uniquely defined by an almost invariant TCRα chain paired with a restricted TCRβ chain repertoire ( Lepore et al, 2014 ; Porcelli et al, 1993 ; Tilloy et al, 1999 ).…”

Section: Introductionmentioning

confidence: 99%

Promiscuous recognition of MR1 drives self-reactive mucosal-associated invariant T cell responses

Chancellor

Simmons

Khanolkar

et al. 2023

Journal of Experimental Medicine

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Mucosal-associated invariant T (MAIT) cells use canonical semi-invariant T cell receptors (TCR) to recognize microbial riboflavin precursors displayed by the antigen-presenting molecule MR1. The extent of MAIT TCR crossreactivity toward physiological, microbially unrelated antigens remains underexplored. We describe MAIT TCRs endowed with MR1-dependent reactivity to tumor and healthy cells in the absence of microbial metabolites. MAIT cells bearing TCRs crossreactive toward self are rare but commonly found within healthy donors and display T-helper-like functions in vitro. Experiments with MR1-tetramers loaded with distinct ligands revealed significant crossreactivity among MAIT TCRs both ex vivo and upon in vitro expansion. A canonical MAIT TCR was selected on the basis of extremely promiscuous MR1 recognition. Structural and molecular dynamic analyses associated promiscuity to unique TCRβ-chain features that were enriched within self-reactive MAIT cells of healthy individuals. Thus, self-reactive recognition of MR1 represents a functionally relevant indication of MAIT TCR crossreactivity, suggesting a potentially broader role of MAIT cells in immune homeostasis and diseases, beyond microbial immunosurveillance.

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

Cited by 17 publications

References 0 publications

An overview on the identification of MAIT cell antigens

An overview on the identification of MAIT cell antigens

Human unconventional T cells in Plasmodium falciparum infection

Promiscuous recognition of MR1 drives self-reactive mucosal-associated invariant T cell responses

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