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
EuropePMC logo PMID: 23613577

Abstract

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)

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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)
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  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)
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  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)
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