High expression of CD26 accurately identifies human bacteria-reactive MR1-restricted MAIT cells.
Mucosa-associated invariant T (MAIT) cells express the semi-invariant T-cell receptor TRAV1-2 and detect a range of bacteria and fungi through the MHC-like molecule MR1. However, knowledge of the function and phenotype of bacteria-reactive MR1-restricted TRAV1-2(+) MAIT cells from human blood is limited. We broadly characterized the function of MR1-restricted MAIT cells in response to bacteria-infected targets and defined a phenotypic panel to identify these cells in the circulation. We demonstrated that bacteria-reactive MR1-restricted T cells shared effector functions of cytolytic effector CD8(+) T cells. By analysing an extensive panel of phenotypic markers, we determined that CD26 and CD161 were most strongly associated with these T cells. Using FACS to sort phenotypically defined CD8(+) subsets we demonstrated that high expression of CD26 on CD8(+)  TRAV1-2(+) cells identified with high specificity and sensitivity, bacteria-reactive MR1-restricted T cells from human blood. CD161(hi) was also specific for but lacked sensitivity in identifying all bacteria-reactive MR1-restricted T cells, some of which were CD161(dim) . Using cell surface expression of CD8, TRAV1-2, and CD26(hi) in the absence of stimulation we confirm that bacteria-reactive T cells are lacking in the blood of individuals with active tuberculosis and are restored in the blood of individuals undergoing treatment for tuberculosis.
Pulmonary & Critical Care Medicine, Oregon Health & Science University, Portland, OR, USA.
Prabhat K
PK
Sharma
KwaZulu-Natal Research Institute for Tuberculosis and HIV, Durban, South Africa.|Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA, USA.
Emily B
EB
Wong
Pulmonary & Critical Care Medicine, Oregon Health & Science University, Portland, OR, USA.
Ruth J
RJ
Napier
Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA, USA.|Division of Infectious Diseases, Johns Hopkins School of Medicine, Baltimore, MD, USA.
William R
WR
Bishai
KwaZulu-Natal Research Institute for Tuberculosis and HIV, Durban, South Africa.|Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA, USA.
Thumbi
T
Ndung'u
KwaZulu-Natal Research Institute for Tuberculosis and HIV, Durban, South Africa.|Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA.|HIV Pathogenesis Programme, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa.
Victoria O
VO
Kasprowicz
Pediatrics, Oregon Health & Science University, Portland, ON, USA.|Molecular Microbiology and Immunology, Oregon Health and Science University, Portland, ON, USA.
Deborah A
DA
Lewinsohn
Pulmonary & Critical Care Medicine, Oregon Health & Science University, Portland, OR, USA.|Molecular Microbiology and Immunology, Oregon Health and Science University, Portland, ON, USA.|Portland VA Medical Center, Portland, ON, USA.
David M
DM
Lewinsohn
Pulmonary & Critical Care Medicine, Oregon Health & Science University, Portland, OR, USA.|Molecular Microbiology and Immunology, Oregon Health and Science University, Portland, ON, USA.|Portland VA Medical Center, Portland, ON, USA.
Marielle C
http://orcid.org/0000-0003-2505-3291
MC
Gold
D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D018819:Dipeptidyl Peptidase 4 / Q000276:immunology* / Q000378:metabolism; D005434:Flow Cytometry; D015395:Histocompatibility Antigens Class I / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D015778:Minor Histocompatibility Antigens; D009092:Mucous Membrane / Q000276:immunology*; D020102:Mycobacterium smegmatis / Q000276:immunology; D055651:NK Cell Lectin-Like Receptor Subfamily B / Q000276:immunology / Q000378:metabolism; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism
D015395:Histocompatibility Antigens Class I; C094840:MR1 protein, human; D015778:Minor Histocompatibility Antigens; D055651:NK Cell Lectin-Like Receptor Subfamily B; D016693:Receptors, Antigen, T-Cell, alpha-beta; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; C042807:DPP4 protein, human; D018819:Dipeptidyl Peptidase 4
MHC; MR1 and MAIT cells; T cells; bacteria; cell surface molecules; human