High expression of CD26 accurately identifies human bacteria‐reactive MR1‐restricted MAIT cells |
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| Authors: | Prabhat K. Sharma Emily B. Wong Ruth J. Napier William R. Bishai Thumbi Ndung'u Victoria O. Kasprowicz Deborah A. Lewinsohn Marielle C. Gold |
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| Affiliation: | 1. Pulmonary & Critical Care Medicine, Oregon Health & Science University, Portland, OR, USA;2. KwaZulu‐Natal Research Institute for Tuberculosis and HIV, Durban, South Africa;3. Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA, USA;4. Division of Infectious Diseases, Johns Hopkins School of Medicine, Baltimore, MD, USA;5. Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA;6. HIV Pathogenesis Programme, Nelson R. Mandela School of Medicine, University of KwaZulu‐Natal, Durban, South Africa;7. Pediatrics, Oregon Health & Science University, Portland, ON, USA;8. Molecular Microbiology and Immunology, Oregon Health and Science University, Portland, ON, USA |
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| Abstract: | 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. CD161hi was also specific for but lacked sensitivity in identifying all bacteria‐reactive MR1‐restricted T cells, some of which were CD161dim. Using cell surface expression of CD8, TRAV1–2, and CD26hi 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. |
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| Keywords: | bacteria cell surface molecules human
MHC
MR1 and MAIT cells T cells |
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