4iiq Citations

The molecular basis for Mucosal-Associated Invariant T cell recognition of MR1 proteins.

Proc. Natl. Acad. Sci. U.S.A. 110 E1771-8 (2013)
Cited: 41 times
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Mucosal-associated invariant T (MAIT) cells are an evolutionarily conserved αβ T-cell lineage that express a semi-invariant T-cell receptor (TCR) restricted to the MHC related-1 (MR1) protein. MAIT cells are dependent upon MR1 expression and exposure to microbes for their development and stimulation, yet these cells can exhibit microbial-independent stimulation when responding to MR1 from different species. We have used this microbial-independent, cross-species reactivity of MAIT cells to define the molecular basis of MAIT-TCR/MR1 engagement and present here a 2.85 Å complex structure of a human MAIT-TCR bound to bovine MR1. The MR1 binding groove is similar in backbone structure to classical peptide-presenting MHC class I molecules (MHCp), yet is partially occluded by large aromatic residues that form cavities suitable for small ligand presentation. The docking of the MAIT-TCR on MR1 is perpendicular to the MR1 surface and straddles the MR1 α1 and α2 helices, similar to classical αβ TCR engagement of MHCp. However, the MAIT-TCR contacts are dominated by the α-chain, focused on the MR1 α2 helix. TCR β-chain contacts are mostly through the variable CDR3β loop that is positioned proximal to the CDR3α loop directly over the MR1 open groove. The elucidation of the MAIT TCR/MR1 complex structure explains how the semi-invariant MAIT-TCR engages the nonpolymorphic MR1 protein, and sheds light onto ligand discrimination by this cell type. Importantly, this structure also provides a critical link in our understanding of the evolution of αβ T-cell recognition of MHC and MHC-like ligands.

Reviews citing this publication (25)

  1. The role of mucosal-associated invariant T cells in infectious diseases. Wong EB, Ndung'u T, Kasprowicz VO. Immunology 150 45-54 (2017)
  2. Immune sensing of microbial glycolipids and related conjugates by T cells and the pattern recognition receptors MCL and Mincle. Smith DG, Williams SJ. Carbohydr. Res. 420 32-45 (2016)
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  5. Structure and function of the non-classical major histocompatibility complex molecule MR1. Krovi SH, Gapin L. Immunogenetics 68 549-559 (2016)
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  7. The Immunology of CD1- and MR1-Restricted T Cells. Mori L, Lepore M, De Libero G. Annu. Rev. Immunol. 34 479-510 (2016)
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  9. Recognition of Vitamin B Precursors and Byproducts by Mucosal Associated Invariant T Cells. Eckle SB, Corbett AJ, Keller AN, Chen Z, Godfrey DI, Liu L, Mak JY, Fairlie DP, Rossjohn J, McCluskey J. J. Biol. Chem. 290 30204-30211 (2015)
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  11. Regulation of Lipid Specific and Vitamin Specific Non-MHC Restricted T Cells by Antigen Presenting Cells and Their Therapeutic Potentials. Salio M, Cerundolo V. Front Immunol 6 388 (2015)
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  13. Early innate responses to pathogens: pattern recognition by unconventional human T-cells. Liuzzi AR, McLaren JE, Price DA, Eberl M. Curr. Opin. Immunol. 36 31-37 (2015)
  14. Adoptive T Cell Therapy Targeting CD1 and MR1. Guo T, Chamoto K, Hirano N. Front Immunol 6 247 (2015)
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  25. Predisposed αβ T cell antigen receptor recognition of MHC and MHC-I like molecules? Eckle SB, Turner SJ, Rossjohn J, McCluskey J. Curr. Opin. Immunol. 25 653-659 (2013)

Articles citing this publication (16)

  1. Crystal structure of Vδ1 T cell receptor in complex with CD1d-sulfatide shows MHC-like recognition of a self-lipid by human γδ T cells. Luoma AM, Castro CD, Mayassi T, Bembinster LA, Bai L, Picard D, Anderson B, Scharf L, Kung JE, Sibener LV, Savage PB, Jabri B, Bendelac A, Adams EJ. Immunity 39 1032-1042 (2013)
  2. Parallel T-cell cloning and deep sequencing of human MAIT cells reveal stable oligoclonal TCRβ repertoire. Lepore M, Kalinichenko A, Colone A, Paleja B, Singhal A, Tschumi A, Lee B, Poidinger M, Zolezzi F, Quagliata L, Sander P, Newell E, Bertoletti A, Terracciano L, De Libero G, Mori L. Nat Commun 5 3866 (2014)
  3. A molecular basis underpinning the T cell receptor heterogeneity of mucosal-associated invariant T cells. 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. J. Exp. Med. 211 1585-1600 (2014)
  4. MR1-restricted MAIT cells display ligand discrimination and pathogen selectivity through distinct T cell receptor usage. 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. J. Exp. Med. 211 1601-1610 (2014)
  5. MAIT recognition of a stimulatory bacterial antigen bound to MR1. López-Sagaseta J, Dulberger CL, McFedries A, Cushman M, Saghatelian A, Adams EJ. J. Immunol. 191 5268-5277 (2013)
  6. Molecular basis of mycobacterial lipid antigen presentation by CD1c and its recognition by αβ T cells. Roy S, Ly D, Li NS, Altman JD, Piccirilli JA, Moody DB, Adams EJ. Proc. Natl. Acad. Sci. U.S.A. 111 E4648-57 (2014)
  7. Functional Heterogeneity and Antimycobacterial Effects of Mouse Mucosal-Associated Invariant T Cells Specific for Riboflavin Metabolites. Sakala IG, Kjer-Nielsen L, Eickhoff CS, Wang X, Blazevic A, Liu L, Fairlie DP, Rossjohn J, McCluskey J, Fremont DH, Hansen TH, Hoft DF. J. Immunol. 195 587-601 (2015)
  8. Metabolic engineering of Salmonella vaccine bacteria to boost human Vγ2Vδ2 T cell immunity. Workalemahu G, Wang H, Puan KJ, Nada MH, Kuzuyama T, Jones BD, Jin C, Morita CT. J. Immunol. 193 708-721 (2014)
  9. MR1-restricted mucosal-associated invariant T (MAIT) cells respond to mycobacterial vaccination and infection in nonhuman primates. Greene JM, Dash P, Roy S, McMurtrey C, Awad W, Reed JS, Hammond KB, Abdulhaqq S, Wu HL, Burwitz BJ, Roth BF, Morrow DW, Ford JC, Xu G, Bae JY, Crank H, Legasse AW, Dang TH, Greenaway HY, Kurniawan M, Gold MC, Harriff MJ, Lewinsohn DA, Park BS, Axthelm MK, Stanton JJ, Hansen SG, Picker LJ, Venturi V, Hildebrand W, Thomas PG, Lewinsohn DM, Adams EJ, Sacha JB. Mucosal Immunol 10 802-813 (2017)
  10. Restricting nonclassical MHC genes coevolve with TRAV genes used by innate-like T cells in mammals. Boudinot P, Mondot S, Jouneau L, Teyton L, Lefranc MP, Lantz O. Proc. Natl. Acad. Sci. U.S.A. 113 E2983-92 (2016)
  11. Multiple layers of heterogeneity and subset diversity in human MAIT cell responses to distinct microorganisms and to innate cytokines. Dias J, Leeansyah E, Sandberg JK. Proc. Natl. Acad. Sci. U.S.A. 114 E5434-E5443 (2017)
  12. A 'GEM' of a cell. Kronenberg M, Zajonc DM. Nat. Immunol. 14 694-695 (2013)
  13. Modeling T cell receptor recognition of CD1-lipid and MR1-metabolite complexes. Pierce BG, Vreven T, Weng Z. BMC Bioinformatics 15 319 (2014)
  14. Cell surface expression of MR1B, a splice variant of the MHC class I-related molecule MR1, revealed with antibodies. Yamaguchi H, Tsukamoto K, Hashimoto K. Biochem. Biophys. Res. Commun. 443 422-427 (2014)
  15. T-cell receptor repertoire of human peripheral CD161hiTRAV1-2+ MAIT cells revealed by next generation sequencing and single cell analysis. Held K, Beltrán E, Moser M, Hohlfeld R, Dornmair K. Hum. Immunol. 76 607-614 (2015)
  16. Mucosal-associated invariant T cells are reduced and functionally immature in the peripheral blood of primary Sjögren's syndrome patients. Wang JJ, Macardle C, Weedon H, Beroukas D, Banovic T. Eur. J. Immunol. 46 2444-2453 (2016)