Preferential recognition of a microbial metabolite by human Vγ2Vδ2 T cells

Kia Joo Puan, Chenggang Jin, Hong Wang, Ghanashyam Sarikonda, Amy M. Raker, Hoi K. Lee, Megan I. Samuelson, Elisabeth Märker-Hermann, Ljiljana Pasa-Tolic, Edward Nieves, José Luis Giner, Tomohisa Kuzuyama, Craig T. Morita

Research output: Contribution to journalArticle

60 Citations (Scopus)

Abstract

Human Vγ2Vδ2 T cells are stimulated by prenyl pyrophosphates, such as isopentenyl pyrophosphate (IPP), and play important roles in mediating immunity against microbial pathogens and have potent anti-tumor activity. (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMBPP) has been identified as a metabolite in the 2-C-methyl-D-erythritol-4 phosphate (MEP) pathway for isoprenoid biosynthesis that is used by many bacteria and protozoan parasites. We find that HMBPP is the major Vγ2Vδ2 T-cell antigen for many bacteria, including Mycobacterium tuberculosis, Yersinia enterocolitica and Escherichia coli. HMBPP was a 30 000-fold more potent antigen than IPP. Using mutant bacteria, we show that bacterial antigen levels for Vγ2Vδ2 T cells are controlled by MEP pathway enzymes and find no evidence for the production of 3-formyl-1-butyl pyrophosphate. Moreover, HMBPP reactivity required only germ line-encoded Vγ2Vδ2 TCR elements and is present at birth. Importantly, we show that bacterial HMBPP levels correlated with their ability to expand Vγ2Vδ2 T cells in vivo upon engraftment into severe combined immunodeficiency-beige mice. Thus, the production of HMBPP by a microbial-specific isoprenoid pathway plays a major role in determining whether bacteria will stimulate Vγ2Vδ2 T cells in vivo. This preferential stimulation by a common microbial isoprenoid metabolite allows Vγ2Vδ2 T cells to respond to a broad array of pathogens using this pathway.

Original languageEnglish (US)
Pages (from-to)657-673
Number of pages17
JournalInternational Immunology
Volume19
Issue number5
DOIs
StatePublished - May 2007

Fingerprint

T-Lymphocytes
Terpenes
Bacteria
Bacterial Antigens
Severe Combined Immunodeficiency
Yersinia enterocolitica
Diphosphates
Viral Tumor Antigens
Mycobacterium tuberculosis
Germ Cells
diphosphoric acid
Immunity
Parasites
Parturition
Escherichia coli
Antigens
Enzymes
Neoplasms
isopentenyl pyrophosphate
2-C-methylerythritol 4-phosphate

Keywords

  • γδ T cells
  • 2-C-methyl-D-erythritol-4 phosphate pathway
  • Microbial immunity
  • Prenyl pyrophosphate antigens

ASJC Scopus subject areas

  • Immunology

Cite this

Puan, K. J., Jin, C., Wang, H., Sarikonda, G., Raker, A. M., Lee, H. K., ... Morita, C. T. (2007). Preferential recognition of a microbial metabolite by human Vγ2Vδ2 T cells. International Immunology, 19(5), 657-673. https://doi.org/10.1093/intimm/dxm031

Preferential recognition of a microbial metabolite by human Vγ2Vδ2 T cells. / Puan, Kia Joo; Jin, Chenggang; Wang, Hong; Sarikonda, Ghanashyam; Raker, Amy M.; Lee, Hoi K.; Samuelson, Megan I.; Märker-Hermann, Elisabeth; Pasa-Tolic, Ljiljana; Nieves, Edward; Giner, José Luis; Kuzuyama, Tomohisa; Morita, Craig T.

In: International Immunology, Vol. 19, No. 5, 05.2007, p. 657-673.

Research output: Contribution to journalArticle

Puan, KJ, Jin, C, Wang, H, Sarikonda, G, Raker, AM, Lee, HK, Samuelson, MI, Märker-Hermann, E, Pasa-Tolic, L, Nieves, E, Giner, JL, Kuzuyama, T & Morita, CT 2007, 'Preferential recognition of a microbial metabolite by human Vγ2Vδ2 T cells', International Immunology, vol. 19, no. 5, pp. 657-673. https://doi.org/10.1093/intimm/dxm031
Puan, Kia Joo ; Jin, Chenggang ; Wang, Hong ; Sarikonda, Ghanashyam ; Raker, Amy M. ; Lee, Hoi K. ; Samuelson, Megan I. ; Märker-Hermann, Elisabeth ; Pasa-Tolic, Ljiljana ; Nieves, Edward ; Giner, José Luis ; Kuzuyama, Tomohisa ; Morita, Craig T. / Preferential recognition of a microbial metabolite by human Vγ2Vδ2 T cells. In: International Immunology. 2007 ; Vol. 19, No. 5. pp. 657-673.
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AU - Raker, Amy M.

AU - Lee, Hoi K.

AU - Samuelson, Megan I.

AU - Märker-Hermann, Elisabeth

AU - Pasa-Tolic, Ljiljana

AU - Nieves, Edward

AU - Giner, José Luis

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AU - Morita, Craig T.

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