Recognition of mycobacterial antigens by γδ T cells

ABSTRACT Mycobacterium tuberculosis readily activates both CD4+ and Vδ2+ γδ T cells. Despite similarity in function, these T-cell subsets differ in the antigens they recognize and the manners in which these antigens are presented byM. tuberculosis-infected monocytes. We investigated mechanisms of antigen processing of M. tuberculosisantigens to human CD4 and γδ T cells by monocytes. Initial uptake of M. tuberculosis bacilli and subsequent processing were required for efficient presentation not only to CD4 T cells but also to Vδ2+ γδ T cells. For γδ T cells, recognition ofM. tuberculosis-infected monocytes was dependent on Vδ2+ T-cell-receptor expression. Recognition of M. tuberculosis antigens by CD4+ T cells was restricted by the class II major histocompatibility complex molecule HLA-DR. Processing of M. tuberculosis bacilli for Vδ2+ γδ T cells was inhibitable by Brefeldin A, whereas processing of soluble mycobacterial antigens for γδ T cells was not sensitive to Brefeldin A. Processing of M. tuberculosis bacilli for CD4+ T cells was unaffected by Brefeldin A. Lysosomotropic agents such as chloroquine and ammonium chloride did not affect the processing of M. tuberculosisbacilli for CD4+ and γδ T cells. In contrast, both inhibitors blocked processing of soluble mycobacterial antigens for CD4+ T cells. Chloroquine and ammonium chloride insensitivity of processing of M. tuberculosis bacilli was not dependent on the viability of the bacteria, since processing of both formaldehyde-fixed dead bacteria and mycobacterial antigens covalently coupled to latex beads was chloroquine insensitive. Thus, the manner in which mycobacterial antigens were taken up by monocytes (particulate versus soluble) influenced the antigen processing pathway for CD4+ and γδ T cells.

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Activation of γδ T cells by mycobacterial antigens in rheumatoid arthritis

Microbes and Infection ◽

10.1016/s1286-4579(99)80034-3 ◽

1999 ◽

Vol 1 (3) ◽

pp. 197-202 ◽

Cited By ~ 11

Author(s):

Joseph Holoshitz

Keyword(s):

Rheumatoid Arthritis ◽

T Cells ◽

Γδ T Cells ◽

Mycobacterial Antigens

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Human T-bet governs innate and innate-like adaptive IFN-γ immunity against mycobacteria

10.1101/2020.08.31.274589 ◽

2020 ◽

Cited By ~ 1

Author(s):

Rui Yang ◽

Federico Mele ◽

Lisa Worley ◽

David Langlais ◽

Jérémie Rosain ◽

...

Keyword(s):

T Cells ◽

T Lymphocytes ◽

Target Genes ◽

Γδ T Cells ◽

Chromatin Accessibility ◽

Mycobacterial Disease ◽

Inborn Errors ◽

Ifn Γ ◽

Low Levels ◽

Mycobacterial Antigens

SummaryInborn errors of human IFN-γ immunity underlie mycobacterial disease. We report a patient with mycobacterial disease due to an inherited deficiency of the transcription factor T-bet. This deficiency abolishes the expression of T-bet target genes, including IFNG, by altering chromatin accessibility and DNA methylation in CD4+ T cells. The patient has profoundly diminished counts of mycobacterial-reactive circulating NK, invariant NKT (iNKT), mucosal-associated invariant T (MAIT), and Vδ2+ γδ T lymphocytes, and of non-mycobacterial-reactive classic TH1 lymphocytes, the remainders of which also produce abnormally low amounts of IFN-γ. Other IFN-γ-producing lymphocyte subsets however develop normally, but with low levels of IFN-γ production, with exception of Vδ2− γδ T lymphocytes, which produce normal amounts of IFN-γ in response to non-mycobacterial stimulation, and non-classic TH1 (TH1*) lymphocytes, which produce IFN-γ normally in response to mycobacterial antigens. Human T-bet deficiency thus underlies mycobacterial disease by preventing the development of, and IFN-γ production by, innate (NK) and innate-like adaptive lymphocytes (iNKT, MAIT, and Vδ2+ γδ T cells), with mycobacterial-specific, IFN-γ-producing, purely adaptive αβ TH1* cells unable to compensate for this deficit.

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