High expression of CD26 accurately identifies human bacteria-reactive MR1-restricted MAIT cells

Prabhat K. Sharma, Emily B. Wong, Ruth J. Napier, William R. Bishai, Thumbi Ndung'u, Victoria O. Kasprowicz, Deborah A. Lewinsohn, David M. Lewinsohn, Marielle C. Gold

Research output: Contribution to journalArticlepeer-review

69 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)443-453
Number of pages11
JournalImmunology
Volume145
Issue number3
DOIs
StatePublished - Jul 1 2015

Keywords

  • Bacteria
  • Cell surface molecules
  • Human
  • MHC
  • MR1 and MAIT cells
  • T cells

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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