ArticleThe Journal of experimental medicine2022
CD8 coreceptor engagement of MR1 enhances antigen responsiveness by human MAIT and other MR1-reactive T cells.
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Article in The Journal of experimental medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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30citing papers in PubMed
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30 citing papers in PubMed, 44 citations in OpenAlex.
- 4-1BB Expression and Signaling Regulates MAIT Cell Activation and Effector Functions.Immunology and cell biology · 2026Article
- Allelic variation alters expression and antigen presentation of MR1 allomorphs.The Journal of biological chemistry · 2026Article
- Immune and metabolic signatures characterise constipation-driven endophenotypes in Parkinson's disease.NPJ Parkinson's disease · 2025Article
- CD4+ mucosal-associated invariant T cells express highly diverse T cell receptors.Journal of immunology (Baltimore, Md. : 1950) · 2025Article
- Human MAIT cells undergo clonal selection and expansion during thymic maturation and aging.Experimental & molecular medicine · 2025Article
- Molecular Insights Into MR1-Mediated T Cell Immunity: Lessons Learned and Unanswered Questions.Immunological reviews · 2025Review
- Defenders or defectors: mucosal-associated invariant T cells in autoimmune diseases.Current opinion in immunology · 2025Review
- MAIT cell homing in intestinal homeostasis and inflammation.Science advances · 2025Review
- Immune Checkpoint Receptor Expression Profiles of MAIT Cells in Moderate and Severe COVID-19.Scandinavian journal of immunology · 2025Article
- MAIT cells: Conserved watchers on the wall.The Journal of experimental medicine · 2025Review
- Control of MAIT cell functions by cytokines in health and disease.Frontiers in immunology · 2025Review
- Mucosal-associated invariant T (MAIT) cell responses inOxford open immunology · 2025Article
- MR1 presents vitamin B6-related compounds for recognition by MR1-reactive T cells.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Article
- MAIT cell heterogeneity across paired human tissues reveals specialization of distinct regulatory and enhanced effector profiles.Science immunology · 2024Article
- MAIT cell activation and recruitment in inflammation and tissue damage in acute appendicitis.Science advances · 2024Article
- Pathways and mechanisms of CD4Trends in immunology · 2024Review
- MR1 antigen presentation to MAIT cells and other MR1-restricted T cells.Nature reviews. Immunology · 2024Review
- Inflammation and Microbial Translocation Correlate with Reduced MAIT Cells in People with HIV.Pathogens & immunity · 2024Article
- Antibody-mediated depletion of select leukocyte subsets in blood and tissue of nonhuman primates.Frontiers in immunology · 2024Article
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Authors and funding
32 authors at 4 institutions in 3 countries.
Michael N T SouterDepartment of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.ORCID 0000-0002-1459-7923
Wael AwadInfection and Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Melbourne, Australia.ORCID 0000-0002-7597-2133
Shihan LiDepartment of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.ORCID 0000-0003-3207-7064
Troi J PediongcoDepartment of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.ORCID 0000-0002-0599-8119
Bronwyn S MeehanDepartment of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.ORCID 0000-0001-7368-2979
Lucy J MeehanDepartment of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.ORCID 0000-0001-8638-644X
Zehua TianDepartment of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.ORCID 0000-0002-5105-9614
Zhe ZhaoDepartment of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.ORCID 0000-0003-1009-324X
Huimeng WangDepartment of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.ORCID 0000-0003-0226-3982
Adam NelsonDepartment of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.ORCID 0000-0002-5897-791X
Jérôme Le NoursInfection and Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Melbourne, Australia.ORCID 0000-0002-2221-7636
Yogesh KhandokarInfection and Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Melbourne, Australia.ORCID 0000-0002-4630-8508
T PraveenaInfection and Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Melbourne, Australia.ORCID 0000-0002-2665-450X
Jacinta WubbenInfection and Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Melbourne, Australia.ORCID 0000-0003-1726-809X
Jie LinDepartment of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.ORCID 0000-0002-7741-7395
Lucy C SullivanDepartment of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.ORCID 0000-0003-2907-4989
George O LovreczBiomedical Manufacturing, Commonwealth Scientific and Industrial Research Organisation, Melbourne, Australia.ORCID 0000-0001-9977-5065
Jeffrey Y W MakDivision of Chemistry and Structural Biology, Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia.ORCID 0000-0002-8011-4539
Ligong LiuDivision of Chemistry and Structural Biology, Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia.ORCID 0000-0002-2693-1896
Lyudmila KostenkoDepartment of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.ORCID 0000-0002-8466-7966
Katherine KedzierskaDepartment of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.ORCID 0000-0001-6141-335X
Alexandra J CorbettDepartment of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.ORCID 0000-0003-1618-4337
David P FairlieDivision of Chemistry and Structural Biology, Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia.ORCID 0000-0002-7856-8566
Andrew G BrooksDepartment of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.ORCID 0000-0002-4085-9683
Nicholas A GherardinDepartment of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.ORCID 0000-0003-4690-2571
Adam P UldrichDepartment of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.ORCID 0000-0002-6350-5976
Zhenjun ChenDepartment of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.ORCID 0000-0003-1205-683X
Jamie RossjohnInfection and Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Melbourne, Australia.ORCID 0000-0002-2020-7522
Dale I GodfreyDepartment of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.ORCID 0000-0002-3009-5472
James McCluskeyDepartment of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.ORCID 0000-0002-8597-815X
Daniel G PellicciDepartment of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.ORCID 0000-0001-5305-2398
Sidonia B G EckleDepartment of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.ORCID 0000-0003-0766-171X
The University of Melbourne · AUMonash University · AUThe University of Queensland · AUCommonwealth Scientific and Industrial Research Organisation · AU
Funding
Investigating the basis of MAIT cell antigen potencyR01AI148407 · NIAID · UNIVERSITY OF MELBOURNE · PI MCCLUSKEY, JAMES · 2020 to 2024
$2.7MAllergy and Immunology Foundation of AustralasiaARC Centre of Excellence CE140100011ARC Discovery Early Career Research Award DE220101491ARC Future Fellowship FT160100074Australian Postgraduate AwardAustralian Research Council FT160100074CSL Centenary FellowshipNational Health and Medical Research Council 1173871NIAID NIH HHS R01 AI148407NIH HHS RO1 AI148407-01A1University of Melbourne
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.
Indexed as
Mucosal-Associated Invariant T CellsReceptors, Antigen, T-Cell, alpha-betaAntigensCD8 AntigensCD8-Positive T-LymphocytesHistocompatibility Antigens Class IHumansMinor Histocompatibility AntigensAntigensCD8 AntigensHistocompatibility Antigens Class IMinor Histocompatibility AntigensMR1 protein, humanReceptors, Antigen, T-Cell, alpha-beta
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