Human mucosal associated invariant T cells detect bacterially infected cells.
Control of infection with Mycobacterium tuberculosis (Mtb) requires Th1-type immunity, of which CD8+ T cells play a unique role. High frequency Mtb-reactive CD8+ T cells are present in both Mtb-infected and uninfected humans. We show by limiting dilution analysis that nonclassically restricted CD8+ T cells are universally present, but predominate in Mtb-uninfected individuals. Interestingly, these Mtb-reactive cells expressed the Valpha7.2 T-cell receptor (TCR), were restricted by the nonclassical MHC (HLA-Ib) molecule MR1, and were activated in a transporter associated with antigen processing and presentation (TAP) independent manner. These properties are all characteristics of mucosal associated invariant T cells (MAIT), an "innate" T-cell population of previously unknown function. These MAIT cells also detect cells infected with other bacteria. Direct ex vivo analysis demonstrates that Mtb-reactive MAIT cells are decreased in peripheral blood mononuclear cells (PBMCs) from individuals with active tuberculosis, are enriched in human lung, and respond to Mtb-infected MR1-expressing lung epithelial cells. Overall, these findings suggest a generalized role for MAIT cells in the detection of bacterially infected cells, and potentially in the control of bacterial infection.
Gold
Marielle C
MC
Division of Pulmonary and Critical Care Medicine, Oregon Health & Science University, Portland, Oregon, United States of America. goldm@ohsu.edu
Cerri
Stefania
S
Smyk-Pearson
Susan
S
Cansler
Meghan E
ME
Vogt
Todd M
TM
Delepine
Jacob
J
Winata
Ervina
E
Swarbrick
Gwendolyn M
GM
Chua
Wei-Jen
WJ
Yu
Yik Y L
YY
Lantz
Olivier
O
Cook
Matthew S
MS
Null
Megan D
MD
Jacoby
David B
DB
Harriff
Melanie J
MJ
Lewinsohn
Deborah A
DA
Hansen
Ted H
TH
Lewinsohn
David M
DM
D000595:Amino Acid Sequence; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002999:Clone Cells; D022801:Complementarity Determining Regions; D003429:Cross Reactions; D006680:HLA Antigens / Q000276:immunology; D006801:Humans; D008969:Molecular Sequence Data; D009092:Mucous Membrane / Q000276:immunology*; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000737:chemistry / Q000276:immunology
D022801:Complementarity Determining Regions; D006680:HLA Antigens; D011948:Receptors, Antigen, T-Cell