Skip to main content
Log in

MAIT, MR1, microbes and riboflavin: a paradigm for the co-evolution of invariant TCRs and restricting MHCI-like molecules?

Immunogenetics Aims and scope Submit manuscript

Abstract

MAIT cells express an invariant TCR that recognizes non-peptidic microbial antigens presented by the non-polymorphic MHCI-like molecule, MR1. We briefly describe how the antigens recognized by MAIT cells are generated from an unstable precursor of the riboflavin (Vitamin B2) biosynthesis pathway, as well as the main features of MAIT cells in comparison with other related T cell subsets. In silico analysis of bacterial genomes shows that the riboflavin biosynthesis pathway is highly prevalent in all groups of Prokaryotes with, however, notable exceptions. We discuss the putative functions and the evolution of the MAIT/MR1 couple: it appeared in the ancestors of mammals and is highly conserved across this group, but was independently lost in three orders. We describe the four instances of known invariant TCR and MHC-I-like molecules encountered in Vertebrates. Both T cells bearing semi-invariant TCR and the associated, evolutionarily conserved MHC-I related molecules have been found in mammals or in amphibians, which suggests that other MHC1-like/invariant TCR couples might be present in other classes of Vertebrates to detect generic microbial compounds. This allows us to discuss how the recognition of riboflavin precursor derivatives by the MAIT TCR may be a way to detect invasive microbes in specific organs, and may epitomize other invariant T cell systems across vertebrates.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  • Abbas CA, Sibirny AA (2011) Genetic control of biosynthesis and transport of riboflavin and flavin nucleotides and construction of robust biotechnological producers. Microbiol Mol Biol Rev 75:321–360

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Annibali V, Ristori G, Angelini DF, Serafini B, Mechelli R, Cannoni S, Romano S, Paolillo A, Abderrahim H, Diamantini A, Borsellino G, Aloisi F, Battistini L, Salvetti M (2010) CD161highCD8 + T cells bear pathogenetic potential in multiple sclerosis. Brain 134:542–554

    Article  Google Scholar 

  • Ashour J, Hondalus MK (2003) Phenotypic mutants of the intracellular actinomycete Rhodococcus equi created by in vivo Himar1 transposon mutagenesis. J Bacteriol 185:2644–2652

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Becker JM, Kauffman SJ, Hauser M, Huang L, Lin M, Sillaots S, Jiang B, Xu D, Roemer T (2010) Pathway analysis of Candida albicans survival and virulence determinants in a murine infection model. Proc Natl Acad Sci U S A 107:22044–22049

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bereswill S, Fassbinder F, Volzing C, Covacci A, Haas R, Kist M (1998) Hemolytic properties and riboflavin synthesis of helicobacter pylori: cloning and functional characterization of the ribA gene encoding GTP-cyclohydrolase II that confers hemolytic activity to Escherichia coli. Med Microbiol Immunol 186:177–187

    Article  CAS  PubMed  Google Scholar 

  • Bonomi HR, Marchesini MI, Klinke S, Ugalde JE, Zylberman V, Ugalde RA, Comerci DJ, Goldbaum FA (2010) An atypical riboflavin pathway is essential for Brucella abortus virulence. PLoS One 5:e9435

    Article  PubMed  PubMed Central  Google Scholar 

  • Boudinot P, Mondot S, Jouneau L, Teytonc L, Lefranc M-P, Lantz O (2016) Restricting non-classical MHC genes co-evolve with TRAV genes used by innate like T cells in mammals. Proc Natl Acad Sci U S A 113(21):E2983–E2992

    Article  CAS  PubMed  Google Scholar 

  • Caporaso JG, Bittinger K, Bushman FD, DeSantis TZ, Andersen GL, Knight R (2010) PyNAST: a flexible tool for aligning sequences to a template alignment. Bioinformatics 26:266–267

    Article  CAS  PubMed  Google Scholar 

  • Corbett AJ, Eckle SB, Birkinshaw RW, Liu L, Patel O, Mahony J, Chen Z, Reantragoon R, Meehan B, Cao H, Williamson NA, Strugnell RA, Van Sinderen D, Mak JY, Fairlie DP, Kjer-Nielsen L, Rossjohn J, McCluskey J (2014) T-cell activation by transitory neo-antigens derived from distinct microbial pathways. Nature 509:361–365

    Article  CAS  PubMed  Google Scholar 

  • Cui Y, Franciszkiewicz K, Mburu YK, Mondot S, Le Bourhis L, Premel V, Martin E, Kachaner A, Duban L, Ingersoll MA, Rabot S, Jaubert J, De Villartay JP, Soudais C, Lantz O (2015) Mucosal-associated invariant T cell-rich congenic mouse strain allows functional evaluation. J Clin Invest 125:4171–4185

    Article  PubMed  PubMed Central  Google Scholar 

  • DeSantis TZ, Hugenholtz P, Larsen N, Rojas M, Brodie EL, Keller K, Huber T, Dalevi D, Hu P, Andersen GL (2006) Greengenes, a chimera-checked 16S rRNA gene database and workbench compatible with ARB. Appl Environ Microbiol 72:5069–5072

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • DiGiulio DB, Callahan BJ, McMurdie PJ, Costello EK, Lyell DJ, Robaczewska A, Sun CL, Goltsman DS, Wong RJ, Shaw G, Stevenson DK, Holmes SP, Relman DA (2015) Temporal and spatial variation of the human microbiota during pregnancy. Proc Natl Acad Sci U S A 112:11060–11065

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Du Pasquier L, Zucchetti I, De Santis R (2004) Immunoglobulin superfamily receptors in protochordates: before RAG time. Immunol Rev 198:233–248

    Article  PubMed  Google Scholar 

  • Dusseaux M, Martin E, Serriari N, Peguillet I, Premel V, Louis D, Milder M, Le Bourhis L, Soudais C, Treiner E, Lantz O (2011) Human MAIT cells are xenobiotic resistant, tissue-targeted, CD161hi IL-17 secreting T cells. Blood 117:1250–1259

    Article  CAS  PubMed  Google Scholar 

  • Eckle SB, Birkinshaw RW, Kostenko L, Corbett AJ, McWilliam HE, Reantragoon R, Chen Z, Gherardin NA, Beddoe T, Liu L, Patel O, Meehan B, Fairlie DP, Villadangos JA, Godfrey DI, Kjer-Nielsen L, McCluskey J, Rossjohn J (2014) A molecular basis underpinning the T cell receptor heterogeneity of mucosal-associated invariant T cells. J Exp Med 211:1585–1600

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Edholm ES, Albertorio Saez LM, Gill AL, Gill SR, Grayfer L, Haynes N, Myers JR, Robert J (2013) Nonclassical MHC class I-dependent invariant T cells are evolutionarily conserved and prominent from early development in amphibians. Proc Natl Acad Sci U S A 110:14342–14347

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Edholm ES, Goyos A, Taran J, De Jesus AF, Ohta Y, Robert J (2014a) Unusual evolutionary conservation and further species-specific adaptations of a large family of nonclassical MHC class Ib genes across different degrees of genome ploidy in the amphibian subfamily Xenopodinae. Immunogenetics 66:411–426

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Edholm ES, Grayfer L, Robert J (2014b) Evolution of nonclassical MHC-dependent invariant T cells. Cell Mol Life Sci 71:4763–4780

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Edholm ES, Grayfer L, De Jesus AF, Robert J (2015) Nonclassical MHC-restricted invariant Valpha6 T cells are critical for efficient early innate antiviral immunity in the amphibian Xenopus laevis. J Immunol 195:576–586

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fan X, Rudensky AY (2016) Hallmarks of tissue-resident lymphocytes. Cell 164:1198–1211

    Article  CAS  PubMed  Google Scholar 

  • Fischer U, Dijkstra JM, Kollner B, Kiryu I, Koppang EO, Hordvik I, Sawamoto Y, Ototake M (2005) The ontogeny of MHC class I expression in rainbow trout (Oncorhynchus mykiss). Fish Shellfish Immunol 18:49–60

    Article  CAS  PubMed  Google Scholar 

  • Franciszkiewicz F, Salou S, Legoux F, Zhou Q, Cui Y, Bessoles S, Lantz O (2016) MHC class I related molecule, MR1, and Mucosal-Associated Invariant T cells. Immunol Rev 172:120–138

  • Fuller TE, Thacker BJ, Mulks MH (1996) A riboflavin auxotroph of Actinobacillus pleuropneumoniae is attenuated in swine. Infect Immun 64:4659–4664

    CAS  PubMed  PubMed Central  Google Scholar 

  • Georgel P, Radosavljevic M, Macquin C, Bahram S (2011) The non-conventional MHC class I MR1 molecule controls infection by Klebsiella pneumoniae in mice. Mol Immunol 48:769–775

    Article  CAS  PubMed  Google Scholar 

  • Gherardin NA, Keller AN, Woolley RE, Le Nours J, Ritchie DS, Neeson PJ, Birkinshaw RW, Eckle SB, Waddington JN, Liu L, Fairlie DP, Uldrich AP, Pellicci DG, McCluskey J, Godfrey DI, Rossjohn J (2016) Diversity of T Cells Restricted by the MHC Class I-Related Molecule MR1 Facilitates Differential Antigen Recognition. Immunity 44:32–45

  • Gibbs A, Leeansyah E, Introini A, Paquin-Proulx D, Hasselrot K, Andersson E, Broliden K, Sandberg JK, Tjernlund A (2016) MAIT cells reside in the female genital mucosa and are biased towards IL-17 and IL-22 production in response to bacterial stimulation. Mucosal Immunol AOP. doi:10.1038/mi.2016.30

  • Gold MC, Cerri S, Smyk-Pearson S, Cansler ME, Vogt TM, Delepine J, Winata E, Swarbrick GM, Chua WJ, Yu YY, Lantz O, Cook MS, Null MD, Jacoby DB, Harriff MJ, Lewinsohn DA, Hansen TH, Lewinsohn DM (2010) Human mucosal associated invariant T cells detect bacterially infected cells. PLoS Biol 8:e1000407

    Article  PubMed  PubMed Central  Google Scholar 

  • Gold MC, Eid T, Smyk-Pearson S, Eberling Y, Swarbrick GM, Langley SM, Streeter PR, Lewinsohn DA, Lewinsohn DM (2013) Human thymic MR1-restricted MAIT cells are innate pathogen-reactive effectors that adapt following thymic egress. Mucosal Immunol 6:35–44

    Article  CAS  PubMed  Google Scholar 

  • Gold MC, McLaren JE, Reistetter JA, Smyk-Pearson S, Ladell K, Swarbrick GM, Yu YY, Hansen TH, Lund O, Nielsen M, Gerritsen B, Kesmir C, Miles JJ, Lewinsohn DA, Price DA, Lewinsohn DM (2014) MR1-restricted MAIT cells display ligand discrimination and pathogen selectivity through distinct T cell receptor usage. J Exp Med 211:1601–1610

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Goyos A, Sowa J, Ohta Y, Robert J (2011) Remarkable conservation of distinct nonclassical MHC class I lineages in divergent amphibian species. J Immunol 186:372–381

    Article  CAS  PubMed  Google Scholar 

  • Grimaldi D, Le Bourhis L, Sauneuf B, Dechartres A, Rousseau C, Ouaaz F, Milder M, Louis D, Chiche JD, Mira JP, Lantz O, Pene F (2014) Specific MAIT cell behaviour among innate-like T lymphocytes in critically ill patients with severe infections. Intensive Care Med 40:192–201

    Article  CAS  PubMed  Google Scholar 

  • Haase D, Roth O, Kalbe M, Schmiedeskamp G, Scharsack JP, Rosenstiel P, Reusch TB (2013) Absence of major histocompatibility complex class II mediated immunity in pipefish, Syngnathus typhle: evidence from deep transcriptome sequencing. Biol Lett 9:20130044

    Article  PubMed  PubMed Central  Google Scholar 

  • Haynes-Gilmore N, Banach M, Edholm ES, Lord E, Robert J (2014) A critical role of non-classical MHC in tumor immune evasion in the amphibian Xenopus model. Carcinogenesis 35:1807–1813

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Huang S, Martin E, Kim S, Yu L, Soudais C, Fremont DH, Lantz O, Hansen TH (2009) MR1 antigen presentation to mucosal-associated invariant T cells was highly conserved in evolution. Proc Natl Acad Sci U S A 106:8290–8295

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jiang J, Wang X, An H, Yang B, Cao Z, Liu Y, Su J, Zhai F, Wang R, Zhang G, Cheng X (2014) Mucosal-associated invariant T-cell function is modulated by programmed death-1 signaling in patients with active tuberculosis. Am J Respir Crit Care Med 190:329–339

    CAS  PubMed  Google Scholar 

  • Jiang J, Yang B, An H, Wang X, Liu Y, Cao Z, Zhai F, Wang R, Cao Y, Cheng X (2015) Mucosal-associated invariant T cells from patients with tuberculosis exhibit impaired immune response. J Infect 72:338–352

  • Kanehisa M, Goto S (2000) KEGG: Kyoto encyclopedia of genes and genomes. Nucleic Acids Res 28:27–30

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kjer-Nielsen L, Patel O, Corbett AJ, Le Nours J, Meehan B, Liu L, Bhati M, Chen Z, Kostenko L, Reantragoon R, Williamson NA, Purcell AW, Dudek NL, McConville MJ, O’Hair RA, Khairallah GN, Godfrey DI, Fairlie DP, Rossjohn J, McCluskey J (2012) MR1 presents microbial vitamin B metabolites to MAIT cells. Nature 491:717–723

    CAS  PubMed  Google Scholar 

  • Kokubu F, Litman R, Shamblott MJ, Hinds K, Litman GW (1988) Diverse organization of immunoglobulin VH gene loci in a primitive vertebrate. EMBO J 7:3413–3422

    CAS  PubMed  PubMed Central  Google Scholar 

  • Kwon YS, Cho YN, Kim MJ, Jin HM, Jung HJ, Kang JH, Park KJ, Kim TJ, Kee HJ, Kim N, Kee SJ, Park YW (2015a) Mucosal-associated invariant T cells are numerically and functionally deficient in patients with mycobacterial infection and reflect disease activity. Tuberculosis (Edinb) 95:267–274

    Article  CAS  Google Scholar 

  • Kwon YS, Jin HM, Cho YN, Kim MJ, Kang JH, Jung HJ, Park KJ, Kee HJ, Kee SJ, Park YW (2015b) Mucosal-Associated Invariant T Cell Deficiency in Chronic Obstructive Pulmonary Disease. COPD:1–7

  • Le Bourhis L, Martin E, Peguillet I, Guihot A, Froux N, Core M, Levy E, Dusseaux M, Meyssonnier V, Premel V, Ngo C, Riteau B, Duban L, Robert D, Huang S, Rottman M, Soudais C, Lantz O (2010) Antimicrobial activity of mucosal-associated invariant T cells. Nat Immunol 11:701–708

    Article  PubMed  Google Scholar 

  • Le Bourhis L, Mburu YK, Lantz O (2013) MAIT cells, surveyors of a new class of antigen: development and functions. Curr Opin Immunol 25:174–180

    Article  PubMed  Google Scholar 

  • Leeansyah E, Ganesh A, Quigley MF, Sonnerborg A, Andersson J, Hunt PW, Somsouk M, Deeks SG, Martin JN, Moll M, Shacklett BL, Sandberg JK (2013) Activation, exhaustion, and persistent decline of the antimicrobial MR1-restricted MAIT-cell population in chronic HIV-1 infection. Blood 121:1124–1135

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Leeansyah E, Loh L, Nixon DF, Sandberg JK (2014) Acquisition of innate-like microbial reactivity in mucosal tissues during human fetal MAIT-cell development. Nat Commun 5:3143

    Article  PubMed  PubMed Central  Google Scholar 

  • Leeansyah E, Svard J, Dias J, Buggert M, Nystrom J, Quigley MF, Moll M, Sonnerborg A, Nowak P, Sandberg JK (2015) Arming of MAIT cell Cytolytic antimicrobial activity is induced by IL-7 and defective in HIV-1 infection. PLoS Pathog 11:e1005072

    Article  PubMed  PubMed Central  Google Scholar 

  • Leung DT, Bhuiyan TR, Nishat NS, Hoq MR, Aktar A, Rahman MA, Uddin T, Khan AI, Chowdhury F, Charles RC, Harris JB, Calderwood SB, Qadri F, Ryan ET (2014) Circulating mucosal associated invariant T cells are activated in vibrio cholerae O1 infection and associated with lipopolysaccharide antibody responses. PLoS Negl Trop Dis 8:e3076

    Article  PubMed  PubMed Central  Google Scholar 

  • Magalhaes I, Pingris K, Poitou C, Bessoles S, Venteclef N, Kiaf B, Beaudoin L, Da Silva J, Allatif O, Rossjohn J, Kjer-Nielsen L, McCluskey J, Ledoux S, Genser L, Torcivia A, Soudais C, Lantz O, Boitard C, Aron-Wisnewsky J, Larger E, Clement K, Lehuen A (2015) Mucosal-associated invariant T cell alterations in obese and type 2 diabetic patients. J Clin Invest 125:1752–1762

    Article  PubMed  PubMed Central  Google Scholar 

  • Martin E, Treiner E, Duban L, Guerri L, Laude H, Toly C, Premel V, Devys A, Moura IC, Tilloy F, Cherif S, Vera G, Latour S, Soudais C, Lantz O (2009) Stepwise development of MAIT cells in mouse and human. PLoS Biol 7:e54

    Article  PubMed  Google Scholar 

  • Mashhadi Z, Xu H, Grochowski LL, White RH (2010) Archaeal RibL: a new FAD synthetase that is air sensitive. Biochemistry 49:8748–8755

    Article  CAS  PubMed  Google Scholar 

  • Matteucci E, Ghimenti M, Consani C, Di Beo S, Giampietro O (2010) About CD26 CD8 lymphocytes in type 1 diabetes mellitus. Scand J Immunol 71:123–124

    Article  CAS  PubMed  Google Scholar 

  • Meierovics A, Yankelevich WJ, Cowley SC (2013) MAIT cells are critical for optimal mucosal immune responses during in vivo pulmonary bacterial infection. Proc Natl Acad Sci U S A 110:E3119–E3128

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Miyazaki Y, Miyake S, Chiba A, Lantz O, Yamamura T (2011) Mucosal-associated invariant T cells regulate Th1 response in multiple sclerosis. Int Immunol 23:529–535

    Article  CAS  PubMed  Google Scholar 

  • Parham P, Benjamin RJ, Chen BP, Clayberger C, Ennis PD, Krensky AM, Lawlor DA, Littman DR, Norment AM, Orr HT, et al. (1989) Diversity of class I HLA molecules: functional and evolutionary interactions with T cells. Cold Spring Harb Symp Quant Biol 54(Pt 1):529–543

    Article  CAS  PubMed  Google Scholar 

  • Price MN, Dehal PS, Arkin AP (2010) FastTree 2--approximately maximum-likelihood trees for large alignments. PLoS One 5:e9490

    Article  PubMed  PubMed Central  Google Scholar 

  • Rahimpour A, Koay HF, Enders A, Clanchy R, Eckle SB, Meehan B, Chen Z, Whittle B, Liu L, Fairlie DP, Goodnow CC, McCluskey J, Rossjohn J, Uldrich AP, Pellicci DG, Godfrey DI (2015) Identification of phenotypically and functionally heterogeneous mouse mucosal-associated invariant T cells using MR1 tetramers. J Exp Med 212:1095–1108

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ravel J, Gajer P, Abdo Z, Schneider GM, Koenig SS, McCulle SL, Karlebach S, Gorle R, Russell J, Tacket CO, Brotman RM, Davis CC, Ault K, Peralta L, Forney LJ (2011) Vaginal microbiome of reproductive-age women. Proc Natl Acad Sci U S A 108(Suppl 1):4680–4687

    Article  CAS  PubMed  Google Scholar 

  • Reantragoon R, Kjer-Nielsen L, Patel O, Chen Z, Illing PT, Bhati M, Kostenko L, Bharadwaj M, Meehan B, Hansen TH, Godfrey DI, Rossjohn J, McCluskey J (2012) Structural insight into MR1-mediated recognition of the mucosal associated invariant T cell receptor. J Exp Med 209:761–774

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Reantragoon R, Corbett AJ, Sakala IG, Gherardin NA, Furness JB, Chen Z, Eckle SB, Uldrich AP, Birkinshaw RW, Patel O, Kostenko L, Meehan B, Kedzierska K, Liu L, Fairlie DP, Hansen TH, Godfrey DI, Rossjohn J, McCluskey J, Kjer-Nielsen L (2013) Antigen-loaded MR1 tetramers define T cell receptor heterogeneity in mucosal-associated invariant T cells. J Exp Med 210:2305–2320

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Robert J, Edholm ES (2014) A prominent role for invariant T cells in the amphibian Xenopus laevis tadpoles. Immunogenetics 66:513–523

    Article  CAS  PubMed  Google Scholar 

  • Seach N, Guerri L, Le Bourhis L, Mburu Y, Cui Y, Bessoles S, Soudais C, Lantz O (2013) Double-positive thymocytes select mucosal-associated invariant T cells. J Immunol 191:6002–6009

    Article  CAS  PubMed  Google Scholar 

  • Serriari NE, Eoche M, Lamotte L, Fumery M, Marcelo P, Chatelain D, Barre A, Nguyen-Khac E, Lantz O, Dupas JL, Treiner E (2014) Innate mucosal-associated invariant T (MAIT) cells are activated in inflammatory bowel diseases. Clin Exp Immunol 191:6002–6009

    Google Scholar 

  • Shamblott MJ, Litman GW (1989) Genomic organization and sequences of immunoglobulin light chain genes in a primitive vertebrate suggest coevolution of immunoglobulin gene organization. EMBO J 8:3733–3739

    CAS  PubMed  PubMed Central  Google Scholar 

  • Sharma PK, Wong EB, Napier RJ, Bishai WR, Ndung’u T, Kasprowicz VO, Lewinsohn DA, Lewinsohn DM, Gold MC (2015) High expression of CD26 accurately identifies human bacteria-reactive MR1-restricted MAIT cells. Immunology 145:443–453

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Smith DJ, Hill GR, Bell SC, Reid DW (2014) Reduced mucosal associated invariant T-cells are associated with increased disease severity and Pseudomonas Aeruginosa infection in cystic fibrosis. PLoS One 9:e109891

    Article  PubMed  PubMed Central  Google Scholar 

  • Soudais C, Samassa F, Sarkis M, Le Bourhis L, Bessoles S, Blanot D, Herve M, Schmidt F, Mengin-Lecreulx D, Lantz O (2015) In vitro and in vivo analysis of the gram-negative bacteria-derived riboflavin precursor derivatives activating mouse MAIT cells. J Immunol 194:4641–4649

    Article  CAS  PubMed  Google Scholar 

  • Star B, Jentoft S (2012) Why does the immune system of Atlantic cod lack MHC II? BioEssays 34:648–651

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Star B, Nederbragt AJ, Jentoft S, Grimholt U, Malmstrom M, Gregers TF, Rounge TB, Paulsen J, Solbakken MH, Sharma A, Wetten OF, Lanzen A, Winer R, Knight J, Vogel JH, Aken B, Andersen O, Lagesen K, Tooming-Klunderud A, Edvardsen RB, Tina KG, Espelund M, Nepal C, Previti C, Karlsen BO, Moum T, Skage M, Berg PR, Gjoen T, Kuhl H, Thorsen J, Malde K, Reinhardt R, Du L, Johansen SD, Searle S, Lien S, Nilsen F, Jonassen I, Omholt SW, Stenseth NC, Jakobsen KS (2011) The genome sequence of Atlantic cod reveals a unique immune system. Nature 477:207–210

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Treiner E, Duban L, Bahram S, Radosavljevic M, Wanner V, Tilloy F, Affaticati P, Gilfillan S, Lantz O (2003) Selection of evolutionarily conserved mucosal-associated invariant T cells by MR1. Nature 422:164–169

    Article  CAS  PubMed  Google Scholar 

  • Turtle CJ, Delrow J, Joslyn RC, Swanson HM, Basom R, Tabellini L, Delaney C, Heimfeld S, Hansen JA, Riddell SR (2011) Innate signals overcome acquired TCR signaling pathway regulation and govern the fate of human CD161(hi) CD8alpha semi-invariant T cells. Blood 118:2752–2762

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ussher JE, Bilton M, Attwod E, Shadwell J, Richardson R, de Lara C, Mettke E, Kurioka A, Hansen TH, Klenerman P, Willberg CB (2014a) CD161++ CD8+ T cells, including the MAIT cell subset, are specifically activated by IL-12 + IL-18 in a TCR-independent manner. Eur J Immunol 44:195–203

    Article  CAS  PubMed  Google Scholar 

  • Ussher JE, Klenerman P, Willberg CB (2014b) Mucosal-associated invariant T-cells: new players in anti-bacterial immunity. Front Immunol 5:450

    Article  PubMed  PubMed Central  Google Scholar 

  • Van Rhijn I, Kasmar A, de Jong A, Gras S, Bhati M, Doorenspleet ME, de Vries N, Godfrey DI, Altman JD, de Jager W, Rossjohn J, Moody DB (2013) A conserved human T cell population targets mycobacterial antigens presented by CD1b. Nat Immunol 14:706–713

    Article  PubMed  PubMed Central  Google Scholar 

  • Van Rhijn I, Godfrey DI, Rossjohn J, Moody DB (2015) Lipid and small-molecule display by CD1 and MR1. Nat Rev Immunol 15:643–654

    Article  PubMed  Google Scholar 

  • Vitreschak AG, Rodionov DA, Mironov AA, Gelfand MS (2002) Regulation of riboflavin biosynthesis and transport genes in bacteria by transcriptional and translational attenuation. Nucleic Acids Res 30:3141–3151

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Walker LJ, Kang YH, Smith MO, Tharmalingham H, Ramamurthy N, Fleming VM, Sahgal N, Leslie A, Oo Y, Geremia A, Scriba TJ, Hanekom WA, Lauer GM, Lantz O, Adams DH, Powrie F, Barnes E, Klenerman P (2012) Human MAIT and CD8alphaalpha cells develop from a pool of type-17 precommitted CD8+ T cells. Blood 119:422–433

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

We thank F. Legoux for reviewing the manuscript, L. Du Pasquier for reviewing the manuscript and insights, S. Gribaldo and L. Teyton for discussions and K. Franciszkiewicz for Fig. 2.

This work was supported by Institut national de la Recherche Agronomique (INRA), by Institut National de la Santé et de la Recherche Médicale, Institut Curie, Agence Nationale de la Recherche (ANR) (Blanc and Labex DCBIOL and Milieu Intérieur) and ARSEP (Association de la recherche sur la sclérose en plaque). OL’s group is supported by the “Equipe labellisée de la Ligue Contre le Cancer”.

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Pierre Boudinot or Olivier Lantz.

Additional information

This article is published in the Special Issue CD1, MR1, NKT, and MAIT: Evolution and Origins of Non-peptidic Antigen Recognition by T lymphocytes with Guest Editor Dr. Dirk Zajonc

Electronic supplementary material

ESM 1

(PDF 3097 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Mondot, S., Boudinot, P. & Lantz, O. MAIT, MR1, microbes and riboflavin: a paradigm for the co-evolution of invariant TCRs and restricting MHCI-like molecules?. Immunogenetics 68, 537–548 (2016). https://doi.org/10.1007/s00251-016-0927-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00251-016-0927-9

Keywords

Navigation