CD8 coreceptor engagement of MR1 enhances antigen responsiveness by human MAIT and other MR1-reactive T cells-Reference-Cited by-同舟云学术

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

Published:2022-08-26 Issue:9 Volume:219 Page:
ISSN:0022-1007
Container-title:Journal of Experimental Medicine
language:en
Short-container-title:

Author:

Souter Michael N.T.¹^ORCID,Awad Wael²^ORCID,Li Shihan¹^ORCID,Pediongco Troi J.¹^ORCID,Meehan Bronwyn S.¹^ORCID,Meehan Lucy J.¹^ORCID,Tian Zehua¹^ORCID,Zhao Zhe¹^ORCID,Wang Huimeng¹³^ORCID,Nelson Adam¹^ORCID,Le Nours Jérôme²^ORCID,Khandokar Yogesh²^ORCID,Praveena T.²^ORCID,Wubben Jacinta²^ORCID,Lin Jie¹^ORCID,Sullivan Lucy C.¹^ORCID,Lovrecz George O.⁴^ORCID,Mak Jeffrey Y.W.⁵^ORCID,Liu Ligong⁵^ORCID,Kostenko Lyudmila¹^ORCID,Kedzierska Katherine¹^ORCID,Corbett Alexandra J.¹^ORCID,Fairlie David P.⁵^ORCID,Brooks Andrew G.¹^ORCID,Gherardin Nicholas A.¹^ORCID,Uldrich Adam P.¹^ORCID,Chen Zhenjun¹^ORCID,Rossjohn Jamie²⁶^ORCID,Godfrey Dale I.¹^ORCID,McCluskey James¹^ORCID,Pellicci Daniel G.¹⁷^ORCID,Eckle Sidonia B.G.¹^ORCID

Affiliation:

1. Department of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia 1

2. Infection and Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Melbourne, Australia 2

3. State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China 3

4. Biomedical Manufacturing, Commonwealth Scientific and Industrial Research Organisation, Melbourne, Australia 4

5. Division of Chemistry and Structural Biology, Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia 5

6. Institute of Infection and Immunity, School of Medicine, Cardiff University, Cardiff, UK 6

7. Murdoch Children’s Research Institute, Parkville, Melbourne, Australia 7

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, analogous to how it engages MHC-I molecules. CD8αα and CD8αβ enhanced MR1 binding and cytokine production by MAIT cells. Moreover, the CD8–MR1 interaction was critical for the recognition of folate-derived antigens by other MR1-reactive T cells. Together, our findings suggest that both CD8αα and CD8αβ act as functional coreceptors for MAIT and other MR1-reactive T cells.

Funder

Australian Postgraduate Award

Australian Research Council

ARC Discovery Early Career Research Award

ARC Future Fellowship

National Health and Medical Research Council

National Institutes of Health

ARC Centre of Excellence

CSL Centenary Fellowship

Allergy and Immunology Foundation of Australasia

University of Melbourne

Publisher