Accumulation of a potent gammadelta T-cell stimulator after deletion of the lytB gene in Escherichia coli

Eberl, Matthias ORCID: https://orcid.org/0000-0002-9390-5348, Altincicek, B., Kollas, A. K., Sanderbrand, S., Bahr, U., Reichenberg, A., Beck, E., Foster, D., Wiesner, J., Hintz, M. and Jomaa, H. 2002. Accumulation of a potent gammadelta T-cell stimulator after deletion of the lytB gene in Escherichia coli. Immunology 106 (2) , pp. 200-211. 10.1046/j.1365-2567.2002.01414.x

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Abstract

Activation of human Vgamma9/Vdelta2 T cells by many pathogens depends on the presence of small phosphorylated non-peptide compounds derived from the 2-C-methyl-d-erythritol 4-phosphate (MEP) pathway of isoprenoid biosynthesis. We here demonstrate that in Escherichia coli mutants deficient in lytB, an essential gene of the MEP pathway, a potent Vgamma9/Vdelta2 T-cell activator accumulates by a factor of approximately 150 compared to wild-type E. coli. The compound responsible for the strong immunogenicity of this E. coli mutant was subsequently characterized and identified as a small pyrophosphorylated metabolite, with a molecular mass of 262 Da, derived from the MEP pathway. Stimulation of human peripheral blood mononuclear cells (PBMC) with extracts prepared from the lytB-deficient E. coli mutant led to upregulation of T-cell activation markers on the surface of Vgamma9/Vdelta2 T cells as well as proliferation and expansion of Vgamma9/Vdelta2 T cells. This response was dependent on costimulatory growth factors, such as interleukin (IL)-2, IL-15 and IL-21. Significant levels of interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha) were secreted in the presence of IL-2 and IL-15, but not in the presence of IL-21, demonstrating that proliferating phosphoantigen-reactive Vgamma9/Vdelta2 T cells do not necessarily produce proinflammatory cytokines.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine Systems Immunity Research Institute (SIURI)
Subjects:	R Medicine > R Medicine (General) R Medicine > RZ Other systems of medicine
Publisher:	Wiley Blackwell
ISSN:	0019-2805
Last Modified:	27 Oct 2022 09:01
URI:	https://orca.cardiff.ac.uk/id/eprint/64123

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