| Title: |
Preferential recognition of a microbial metabolite by human V{gamma}2V{delta}2 T cells |
| Authors: |
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. |
| Publisher Information: |
Oxford University Press |
| Publication Year: |
2007 |
| Collection: |
HighWire Press (Stanford University) |
| Subject Terms: |
Article |
| Description: |
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. |
| Document Type: |
text |
| File Description: |
text/html |
| Language: |
English |
| Relation: |
http://intimm.oxfordjournals.org/cgi/content/short/dxm031v1; http://dx.doi.org/10.1093/intimm/dxm031 |
| DOI: |
10.1093/intimm/dxm031 |
| Availability: |
http://intimm.oxfordjournals.org/cgi/content/short/dxm031v1; https://doi.org/10.1093/intimm/dxm031 |
| Rights: |
Copyright (C) 2007, The Japanese Society for Immunology |
| Accession Number: |
edsbas.DAB2E28A |
| Database: |
BASE |