CD8 coreceptor engagement of MR1 enhances antigen responsiveness by human MAIT and other MR1-reactive T cells

Michael NT Souter; Wael Awad; Shihan Li; Troi Pediongco; Bronwyn S Meehan; Lucy J Meehan; Zehua Tian; Zhe Zhao; Huimeng Wang; Adam Nelson; Jérôme Le Nours; Yogesh Khandokar; T Praveena; Jacinta Wubben; Jie Lin; Lucy C Sullivan; George Lovrecz; Jeffrey YW Mak; Ligong Liu; Lyudmila Kostenko; Katherine Kedzierska; Alexandra J Corbett; David P Fairlie; Andrew G Brooks; Nicholas A Gherardin; Adam P Uldrich; Zhenjun Chen; Jamie Rossjohn; Dale I Godfrey; James MCCLUSKEY; Daniel G Pellicci; Sidonia BG Eckle

Journal article

CD8 coreceptor engagement of MR1 enhances antigen responsiveness by human MAIT and other MR1-reactive T cells

Michael NT Souter, Wael Awad, Shihan Li, Troi Pediongco, Bronwyn S Meehan, Lucy J Meehan, Zehua Tian, Zhe Zhao, Huimeng Wang, Adam Nelson, Jérôme Le Nours, Yogesh Khandokar, T Praveena, Jacinta Wubben, Jie Lin, Lucy C Sullivan, George Lovrecz, Jeffrey YW Mak, Ligong Liu, Lyudmila Kostenko Show all

Journal of Experimental Medicine | Rockefeller University Press | Published : 2022

DOI: 10.1084/jem.20210828

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Abstract

Mucosal-associated invariant T (MAIT) cells detect microbial infection via recognition of riboflavin-based antigens presented by the major histocompatibility complex class I (MHC-I)-related protein 1 (MR1). Most MAIT cells in human peripheral blood express CD8αα or CD8αβ coreceptors, and the binding site for CD8 on MHC-I molecules is relatively conserved in MR1. Yet, there is no direct evidence of CD8 interacting with MR1 or the functional consequences thereof. Similarly, the role of CD8αα in lymphocyte function remains ill-defined. Here, using newly developed MR1 tetramers, mutated at the CD8 binding site, and by determining the crystal structure of MR1-CD8αα, we show that CD8 engaged MR1, ..

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University of Melbourne Researchers

Michael Souter Author

Shihan Li Author

Bronwyn Meehan Author

Lucy Meehan Author

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Grants

Awarded by National Institutes of Health

Funding Acknowledgements

We also would like to acknowledge the following funding: Australian Postgraduate Award (M.N.T. Souter), Australian Research Council (ARC) Discovery Early Career Research Award (DECRA) fellowship DE220101491 (W. Awad), ARC Future Fellowship FT160100074 (J. Le Nours), National Health andMedical Research Council (NHMRC) of Australia Leadership Investigator Grant 1173871 (K. Kedzierska), ARC Future Fellowship FT160100083 (A.J. Corbett), NHMRC Leadership Investigator Grant 1193745 (A.J. Corbett), Dame Kate Campbell Research Fellowship from The University of Melbourne (A.J. Corbett), NHMRC Leadership Investigator Grant 2009551 (D.P. Fairlie), NHMRCLeadership Investigator Grant 2008981 (J. Rossjohn), NHMRC Senior Principal Research Fellowship 1117766 and NHMRC Leadership Investigator Grant 2008913 (D.I. Godfrey), National Institutes of Health RO1 AI148407-01A1 (J. McCluskey, J. Rossjohn, D.P. Fairlie), ARC Centre of Excellence CE140100011 (J. Rossjohn, D.P. Fairlie, D.I. Godfrey), NHMRC Program Grant 1113293 (J. McCluskey, J. Rossjohn, D.I. Godfrey), CSL Centenary Fellowship (D.G. Pellicci), NHMRC Project Grant APP1144308 (D.G. Pellicci), NHMRC Project Grant APP1140126 (D.I. Godfrey, D.G.Pellicci), ARC DECRA fellowship DE170100407 (S.B.G. Eckle), NHMRC Project Grant APP1157388 (S.B.G. Eckle), 2019 Allergy and Immunology Foundation of Australasia research grant (S.B.G. Eckle), and NHMRC Emerging Leadership Investigator Grant 1196881 (S.B.G. Eckle).