Human TRAV1-2-negative MR1-restricted T cells detect S. pyogenes and alternatives to MAIT riboflavin-based antigens

Erin W Meermeier; Bruno F Laugel; Andrew K Sewell; Alexandra J Corbett; Jamie Rossjohn; James McCluskey; Melanie J Harriff; Tamera Franks; Marielle C Gold; David M Lewinsohn

doi:10.1038/ncomms12506

Human TRAV1-2-negative MR1-restricted T cells detect S. pyogenes and alternatives to MAIT riboflavin-based antigens

Nat Commun. 2016 Aug 16:7:12506. doi: 10.1038/ncomms12506.

Authors

Erin W Meermeier¹, Bruno F Laugel², Andrew K Sewell², Alexandra J Corbett³, Jamie Rossjohn^{2

4

5}, James McCluskey³, Melanie J Harriff^{6

7}, Tamera Franks⁷, Marielle C Gold^{1

6

7}, David M Lewinsohn^{1

6

7}

Affiliations

¹ Department of Molecular Microbiology and Immunology, Oregon Health and Science University, Portland, Oregon 97239 USA.
² Institute of Infection and Immunity, Henry Wellcome Research Institute, Cardiff University School of Medicine, Cardiff CF14 4XN, UK.
³ Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, Victoria 3010, Australia.
⁴ Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Clayton, Victoria 3800, Australia.
⁵ ARC Centre of Excellence in Advanced Molecular Imaging, Monash University, Clayton, Victoria 3800, Australia.
⁶ Department of Pulmonary and Critical Care Medicine, Oregon Health and Science University, Portland, Oregon 97239, USA.
⁷ Department of Research, VA Portland Health Care Center, Portland, Oregon 97239, USA.

Abstract

Mucosal-associated invariant T (MAIT) cells are thought to detect microbial antigens presented by the HLA-Ib molecule MR1 through the exclusive use of a TRAV1-2-containing TCRα. Here we use MR1 tetramer staining and ex vivo analysis with mycobacteria-infected MR1-deficient cells to demonstrate the presence of functional human MR1-restricted T cells that lack TRAV1-2. We characterize an MR1-restricted clone that expresses the TRAV12-2 TCRα, which lacks residues previously shown to be critical for MR1-antigen recognition. In contrast to TRAV1-2(+) MAIT cells, this TRAV12-2-expressing clone displays a distinct pattern of microbial recognition by detecting infection with the riboflavin auxotroph Streptococcus pyogenes. As known MAIT antigens are derived from riboflavin metabolites, this suggests that TRAV12-2(+) clone recognizes unique antigens. Thus, MR1-restricted T cells can discriminate between microbes in a TCR-dependent manner. We postulate that additional MR1-restricted T-cell subsets may play a unique role in defence against infection by broadening the recognition of microbial metabolites.

Publication types

Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

A549 Cells
Antigen Presentation / immunology
Antigens / immunology*
Cell Line
Cells, Cultured
Histocompatibility Antigens Class I / immunology*
Histocompatibility Antigens Class I / metabolism
Host-Pathogen Interactions / immunology
Humans
Minor Histocompatibility Antigens / immunology*
Minor Histocompatibility Antigens / metabolism
Mucosal-Associated Invariant T Cells / immunology
Mucosal-Associated Invariant T Cells / metabolism
Receptors, Antigen, T-Cell, alpha-beta / immunology*
Receptors, Antigen, T-Cell, alpha-beta / metabolism
Riboflavin / immunology*
Riboflavin / metabolism
Streptococcal Infections / diagnosis
Streptococcal Infections / immunology
Streptococcal Infections / microbiology
Streptococcus pyogenes / immunology*
Streptococcus pyogenes / physiology
T-Lymphocyte Subsets / immunology*
T-Lymphocyte Subsets / metabolism

Substances

Antigens
Histocompatibility Antigens Class I
MR1 protein, human
Minor Histocompatibility Antigens
Receptors, Antigen, T-Cell, alpha-beta
Riboflavin

Abstract

Publication types

MeSH terms

Substances

Grants and funding