Immunogenetics

, Volume 65, Issue 2, pp 115–124 | Cite as

Exceptionally high conservation of the MHC class I-related gene, MR1, among mammals

  • Kentaro Tsukamoto
  • Janine E. Deakin
  • Jennifer A. Marshall Graves
  • Keiichiro Hashimoto
Original Paper

Abstract

The major histocompatibility complex (MHC) class I-related gene, MR1, is a non-classical MHC class IA gene and is encoded outside the MHC region. The MR1 is responsible for activation of mucosal-associated invariant T (MAIT) cells expressing semi-invariant T cell receptors in the presence of bacteria, but its ligand has not been identified. A unique characteristic of MR1 is its high evolutionary conservation of the α1 and α2 domains corresponding to the peptide-binding domains of classical MHC class I molecules, showing about 90 % amino acid identity between human and mouse. To clarify the evolutionary history of MR1 and identify more critically conserved residues for the function of MR1, we searched for the MR1 gene using jawed vertebrate genome databases and isolated the MR1 cDNA sequences of marsupials (opossum and wallaby). A comparative genomic analysis indicated that MR1 is only present in placental and marsupial mammals and that the gene organization around MR1 is well conserved among analyzed jawed vertebrates. Moreover, the α1 and α2 domains, especially in amino acid residues presumably shaping a ligand-binding groove, were also highly conserved between placental and marsupial MR1. These findings suggest that the MR1 gene might have been established at its present location in a common ancestor of placental and marsupial mammals and that the shape of the putative ligand-binding groove in MR1 has been maintained, probably for presenting highly conserved component(s) of microbes to MAIT cells.

Keywords

Major histocompatibility complex Non-classical MHC class I MR1 Molecular evolution 

Supplementary material

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References

  1. Adamski FM, King AT, Demmer J (2000) Expression of the Fc receptor in the mammary gland during lactation in the marsupial Trichosurus vulpecula (brushtail possum). Mol Immunol 37:435–444PubMedCrossRefGoogle Scholar
  2. Araki T, Gejyo F, Takagaki K, Haupt H, Schwick HG, Bürgi W, Marti T, Schaller J, Rickli E, Brossmer R (1988) Complete amino acid sequence of human plasma Zn-alpha 2-glycoprotein and its homology to histocompatibility antigens. Proc Natl Acad Sci USA 85:679–683PubMedCrossRefGoogle Scholar
  3. Baker ML, Miller RD (2007) Evolution of mammalian CD1: marsupial CD1 is not orthologous to the eutherian isoforms and is a pseudogene in the opossum Monodelphis domestica. Immunology 121:113–121PubMedCrossRefGoogle Scholar
  4. Bininda-Emonds ORP, Cardillo M, Jones KE, MacPhee RDE, Beck RMD, Grenyer R, Price SA, Vos RA, Gittleman JL, Purvis A (2007) The delayed rise of present-day mammals. Nature 446:507–512PubMedCrossRefGoogle Scholar
  5. Borg NA, Wun KS, Kjer-Nielsen L, Wilce MCJ, Pellicci DG, Koh R, Besra GS, Bharadwaj M, Godfrey DI, McCluskey J, Rossjohn J (2007) CD1d–lipid-antigen recognition by the semi-invariant NKT T-cell receptor. Nature 448:44–49PubMedCrossRefGoogle Scholar
  6. Calabi F, Milstein C (1986) A novel family of human major histocompatibility complex-related genes not mapping to chromosome 6. Nature 323:540–543PubMedCrossRefGoogle Scholar
  7. Consortium TM (1999) Complete sequence and gene map of a human major histocompatibility complex. The MHC sequencing consortium. Nature 401:921–923CrossRefGoogle Scholar
  8. Cosman D, Müllberg J, Sutherland CL, Chin W, Armitage R, Fanslow W, Kubin M, Chalupny NJ (2001) ULBPs, novel MHC class I-related molecules, bind to CMV glycoprotein UL16 and stimulate NK cytotoxicity through the NKG2D receptor. Immunity 14:123–133PubMedCrossRefGoogle Scholar
  9. Dusseaux M, Martin E, Serriari N, Péguillet 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 117:1250–1259PubMedCrossRefGoogle Scholar
  10. Feder JN, Gnirke A, Thomas W, Tsuchihashi Z, Ruddy DA, Basava A, Dormishian F, Domingo R, Ellis MC, Fullan A, Hinton LM, Jones NL, Kimmel BE, Kronmal GS, Lauer P, Lee VK, Loeb DB, Mapa FA, McClelland E, Meyer NC, Mintier GA, Moeller N, Moore T, Morikang E, Prass CE, Quintana L, Starnes SM, Schatzman RC, Brunke KJ, Drayna DT, Risch NJ, Bacon BR, Wolff RK (1996) A novel MHC class I-like gene is mutated in patients with hereditary haemochromatosis. Nat Genet 13:399–408PubMedCrossRefGoogle Scholar
  11. Flajnik MF, Kasahara M (2001) Comparative genomics of the MHC: glimpses into the evolution of the adaptive immune system. Immunity 15:351–362PubMedCrossRefGoogle Scholar
  12. Fukudome K, Esmon CT (1994) Identification, cloning, and regulation of a novel endothelial cell protein C/activated protein C receptor. J Biol Chem 269:26486–26491PubMedGoogle Scholar
  13. Garboczi DN, Ghosh P, Utz U, Fan QR, Biddison WE, Wiley DC (1996) Structure of the complex between human T-cell receptor, viral peptide and HLA-A2. Nature 384:134–141PubMedCrossRefGoogle Scholar
  14. Godfrey DI, Pellicci DG, Patel O, Kjer-Nielsen L, McCluskey J, Rossjohn J (2010) Antigen recognition by CD1d-restricted NKT T cell receptors. Semin Immunol 22:61–67PubMedCrossRefGoogle Scholar
  15. Gold MC, Cerri S, Smyk-Pearson S, Cansler ME, Vogt TM, Delepine J, Winata E, Swarbrick GM, Chua W-J, Yu YYL, 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 (P Marrack, Ed.). PLoS Biol 8:e1000407PubMedCrossRefGoogle Scholar
  16. Goldfinch N, Reinink P, Connelley T, Koets A, Morrison I, Van Rhijn I (2010) Conservation of mucosal associated invariant T (MAIT) cells and the MR1 restriction element in ruminants, and abundance of MAIT cells in spleen. Vet Res 41:62PubMedCrossRefGoogle Scholar
  17. Hashimoto K, Hirai M, Kurosawa Y (1995) A gene outside the human MHC related to classical HLA class I genes. Science 269:693–695PubMedCrossRefGoogle Scholar
  18. Hashimoto K, Hirai M, Kurosawa Y (1997) Identification of a mouse homolog for the human hereditary haemochromatosis candidate gene. Biochem Biophys Res Commun 230:35–39PubMedCrossRefGoogle Scholar
  19. 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 USA 106:8290–8295PubMedCrossRefGoogle Scholar
  20. Jaillon O, Aury J-M, Brunet F, Petit J-L, Stange-Thomann N, Mauceli E, Bouneau L, Fischer C, Ozouf-Costaz C, Bernot A, Nicaud S, Jaffe D, Fisher S, Lutfalla G, Dossat C, Segurens B, Dasilva C, Salanoubat M, Levy M, Boudet N, Castellano S, Anthouard V, Jubin C, Castelli V, Katinka M, Vacherie B, Biémont C, Skalli Z, Cattolico L, Poulain J, De Berardinis V, Cruaud C, Duprat S, Brottier P, Coutanceau J-P, Gouzy J, Parra G, Lardier G, Chapple C, McKernan KJ, McEwan P, Bosak S, Kellis M, Volff J-N, Guigó R, Zody MC, Mesirov J, Lindblad-Toh K, Birren B, Nusbaum C, Kahn D, Robinson-Rechavi M, Laudet V, Schachter V, Quétier F, Saurin W, Scarpelli C, Wincker P, Lander ES, Weissenbach J, Roest Crollius H (2004) Genome duplication in the teleost fish Tetraodon nigroviridis reveals the early vertebrate proto-karyotype. Nature 431:946–957PubMedCrossRefGoogle Scholar
  21. Kasahara M (1997) New insights into the genomic organization and origin of the major histocompatibility complex: role of chromosomal (genome) duplication in the emergence of the adaptive immune system. Hereditas 127:59–65PubMedCrossRefGoogle Scholar
  22. Kasahara M (2007) The 2R hypothesis: an update. Curr Opin Immunol 19:547–552PubMedCrossRefGoogle Scholar
  23. Kasahara M, Watanabe Y, Sumasu M, Nagata T (2002) A family of MHC class I-like genes located in the vicinity of the mouse leukocyte receptor complex. Proc Natl Acad Sci USA 99:13687–13692PubMedCrossRefGoogle Scholar
  24. Kelley J, Walter L, Trowsdale J (2005) Comparative genomics of major histocompatibility complexes. Immunogenetics 56:683–695PubMedCrossRefGoogle Scholar
  25. 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 RAJ, Khairallah GN, Godfrey DI, Fairlie DP, Rossjohn J, McCluskey J (2012) MR1 presents microbial vitamin B metabolites to MAIT cells. Nature. doi:10.1038/nature11605
  26. Kondo M, Maruoka T, Otsuka N, Kasamatsu J, Fugo K, Hanzawa N, Kasahara M (2010) Comparative genomic analysis of mammalian NKG2D ligand family genes provides insights into their origin and evolution. Immunogenetics 62:441–450PubMedCrossRefGoogle Scholar
  27. Larkin MA, Blackshields G, Brown NP, Chenna R, McGettigan PA, McWilliam H, Valentin F, Wallace IM, Wilm A, Lopez R, Thompson JD, Gibson TJ, Higgins DG (2007) Clustal W and Clustal X version 2.0. Bioinformatics 23:2947–2948PubMedCrossRefGoogle Scholar
  28. Le Bourhis L, Martin E, Péguillet I, Guihot A, Froux N, Coré M, Lévy E, Dusseaux M, Meyssonnier V, Premel V, Ngo C, Riteau B, Duban L, Robert D, Rottman M, Soudais C, Lantz O (2010) Antimicrobial activity of mucosal-associated invariant T cells. Nat Immunol 11:701–708PubMedCrossRefGoogle Scholar
  29. 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:e54PubMedCrossRefGoogle Scholar
  30. Maruoka T, Tanabe H, Chiba M, Kasahara M (2005) Chicken CD1 genes are located in the MHC: CD1 and endothelial protein C receptor genes constitute a distinct subfamily of class-I-like genes that predates the emergence of mammals. Immunogenetics 57:590–600PubMedCrossRefGoogle Scholar
  31. Miller MM, Wang C, Parisini E, Coletta RD, Goto RM, Lee SY, Barral DC, Townes M, Roura-Mir C, Ford HL, Brenner MB, Dascher CC (2005) Characterization of two avian MHC-like genes reveals an ancient origin of the CD1 family. Proc Natl Acad Sci USA 102:8674–8679PubMedCrossRefGoogle Scholar
  32. Okamoto N, Kanie O, Huang Y-Y, Fujii R, Watanabe H, Shimamura M (2005) Synthetic alpha-mannosyl ceramide as a potent stimulant for an NKT cell repertoire bearing the invariant Valpha19-Jalpha26 TCR alpha chain. Chem Biol 12:677–683PubMedCrossRefGoogle Scholar
  33. Parra-Cuadrado J, del Moral M, Garc x000ED a-Pav x000ED a P, Seti x000E9 n F, Mart x000ED nez-Naves E (2001) Characterization of the MHC class I-related MR1 locus in nonhuman primates. Immunogenetics 53:643–648Google Scholar
  34. 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(4):761–774PubMedCrossRefGoogle Scholar
  35. Phillips MJ, Bennett TH, Lee MS (2009) Molecules, morphology, and ecology indicate a recent, amphibious ancestry for echidnas. Proc Natl Acad Sci USA 106(40):17089–17094PubMedCrossRefGoogle Scholar
  36. Riegert P, Wanner V, Bahram S (1998) Genomics, isoforms, expression, and phylogeny of the MHC class I-related MR1 gene. J Immunol 161:4066–4077PubMedGoogle Scholar
  37. Rock KL, Goldberg AL (1999) Degradation of cell proteins and the generation of MHC class I-presented peptides. Annu Rev Immunol 17:739–779PubMedCrossRefGoogle Scholar
  38. Salomonsen J, Sørensen MR, Marston DA, Rogers SL, Collen T, van Hateren A, Smith AL, Beal RK, Skjødt K, Kaufman J (2005) Two CD1 genes map to the chicken MHC, indicating that CD1 genes are ancient and likely to have been present in the primordial MHC. Proc Natl Acad Sci USA 102:8668–8673PubMedCrossRefGoogle Scholar
  39. Shimamura M, Huang Y-Y, Okamoto N, Suzuki N, Yasuoka J, Morita K, Nishiyama A, Amano Y, Mishina T (2007) Modulation of Valpha19 NKT cell immune responses by alpha-mannosyl ceramide derivatives consisting of a series of modified sphingosines. Eur J Immunol 37:1836–1844PubMedCrossRefGoogle Scholar
  40. Simister NE, Mostov KE (1989) An Fc receptor structurally related to MHC class I antigens. Nature 337:184–187PubMedCrossRefGoogle Scholar
  41. Tamura K, Peterson D, Peterson N, Stecher G, Nei M, Kumar S (2011) MEGA5: molecular evolutionary genetics analysis using maximum likelihood, evolutionary distance, and maximum parsimony methods. Mol Biol Evol 28:2731–2739PubMedCrossRefGoogle Scholar
  42. Tilloy F, Treiner E, Park SH, Garcia C, Lemonnier F, de La Salle H, Bendelac A, Bonneville M, Lantz O (1999) An invariant T cell receptor alpha chain defines a novel TAP-independent major histocompatibility complex class Ib-restricted alpha/beta T cell subpopulation in mammal. J Exp Med 189:1907–1921PubMedCrossRefGoogle Scholar
  43. 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 422:164–169PubMedCrossRefGoogle Scholar
  44. Vandepoele K, De Vos W, Taylor JS, Meyer A, Van de Peer Y (2004) Major events in the genome evolution of vertebrates: paranome age and size differ considerably between ray-finned fishes and land vertebrates. Proc Natl Acad Sci USA 101:1638–1643PubMedCrossRefGoogle Scholar
  45. Walter L, Günther E (1998) Isolation and molecular characterization of the rat MR1 homologue, a non-MHC-linked class I-related gene. Immunogenetics 47:477–482PubMedCrossRefGoogle Scholar
  46. Yamaguchi H, Hashimoto K (2002) Association of MR1 protein, an MHC class I-related molecule, with beta(2)-microglobulin. Biochem Biophys Res Commun 290:722–729PubMedCrossRefGoogle Scholar
  47. Yamaguchi H, Hirai M, Kurosawa Y, Hashimoto K (1997) A highly conserved major histocompatibility complex class I-related gene in mammals. Biochem Biophys Res Commun 238:697–702PubMedCrossRefGoogle Scholar
  48. Zou Z, Nomura M, Takihara Y, Yasunaga T, Shimada K (1996) Isolation and characterization of retinoic acid-inducible cDNA clones in F9 cells: a novel cDNA family encodes cell surface proteins sharing partial homology with MHC class I molecules. J Biochem 119:319–328PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  • Kentaro Tsukamoto
    • 1
  • Janine E. Deakin
    • 2
  • Jennifer A. Marshall Graves
    • 3
  • Keiichiro Hashimoto
    • 1
  1. 1.Institute for Comprehensive Medical ScienceFujita Health UniversityToyoakeJapan
  2. 2.Division of Evolution, Ecology and Genetics, Research School of BiologyThe Australian National UniversityCanberraAustralia
  3. 3.La Trobe Institute of Molecular SciencesLa Trobe UniversityMelbourneAustralia

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