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 Gold

Research output: Contribution to journalArticlepeer-review

85 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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