Journal article
Human TRAV1-2-negative MR1-restricted T cells detect S. pyogenes and alternatives to MAIT riboflavin-based antigens
EW Meermeier, BF Laugel, AK Sewell, AJ Corbett, J Rossjohn, J McCluskey, MJ Harriff, T Franks, MC Gold, DM Lewinsohn
Nature Communications | NATURE PUBLISHING GROUP | Published : 2016
DOI: 10.1038/ncomms12506
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 S..
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Awarded by National Institute of Allergy and Infectious Diseases
Funding Acknowledgements
We thank Ted Hansen for his generous gift of the alpha-MR1 antibody (26.5), Branch Moody for his generous gift of the alpha-CD1 antibodies, Deborah Lewinsohn, Nicholas Meermeier and Eisa Mahyari for critical reading of the manuscript and Miranda Gilchrist for her FACS expertise. This work was supported by Merit Review Awards #I01 BX001231 (M.C.G.); I01 BX000533 (D.M.L.) from the United States Department of Veterans Affairs Biomedical Laboratory Research and Career Development Award IK2 CX000538 from the U.S. Department of Veterans Affairs Clinical Sciences Research and Development Program (M.C.H.) and resources and the use of facilities at the VA Portland Health Care System; NIH AI078965 (M.C.G.); AI048090, AI048090-15 (D.M.L.); AI078903-05 (E.W.M.); HL83808-05 (E.W.M.); and AI007472-21 (E.W.M.). Disclaimer The contents of this manuscript do not represent the views of the U.S. Department of Veterans Affairs or the United States Government.