HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 276, Issue 19, 15961-15967, May 11, 2001

This Article Full Text Full Text (PDF) All Versions of this Article: 276/19/15961    most recent M008684200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lafont, V. Articles by Favero, J. Search for Related Content PubMed PubMed Citation Articles by Lafont, V. Articles by Favero, J. Social Bookmarking                      What's this?

Isopentenyl Pyrophosphate, a Mycobacterial Non-peptidic Antigen, Triggers Delayed and Highly Sustained Signaling in Human T Lymphocytes without Inducing Down-modulation of T Cell Antigen Receptor^*

Virginie Lafont, Janny Liautard, Magali Sablé-Teychené, Yannis Sainte-Marie, and Jean Favero^§

From INSERM U431, Microbiologie et Pathologie Cellulaire Infectieuse, Université Montpellier 2, Place Eugène Bataillon, cc 100, Montpellier 34095, cedex 5, France

The V9V2 T cell subset, which represents up to 90% of the circulating T cells in humans, was shown to be activated, via the T cell receptor (TcR), by non-peptidic phosphorylated small organic molecules. These phosphoantigens, which are not presented by professional antigen-presenting cells, induce production of high amounts of interferon- and tumor necrosis factor (TNF-). To date, the specific signals triggered by these antigens have not been characterized. Here we analyze proximal and later intracellular signals triggered by isopentenyl pyrophosphate (IPP), a mycobacterial antigen that specifically stimulates V9V2 T cells, and compare these to signals induced by the non-physiological model using an anti-CD3 antibody. During antigenic stimulation we noticed that, except for the proximal p56^lck signal, which is triggered early, the signals appear to be delayed and highly sustained. This delay, which likely accounts for the delay observed in TNF- production, is discussed in terms of the ability of the antigen to cross-link and recruit transducing molecules mostly anchored to lipid rafts. Moreover, we demonstrate that, in contrast to anti-CD3 antibody, IPP does not induce down-modulation of the TcR·CD3 complex, which likely results in the highly sustained signaling and release of high levels of TNF-.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				S. Bessoles, F. Fouret, S. Dudal, G. S. Besra, F. Sanchez, and V. Lafont IL-2 triggers specific signaling pathways in human NKT cells leading to the production of pro- and anti-inflammatory cytokines J. Leukoc. Biol., July 1, 2008; 84(1): 224 - 233. [Abstract] [Full Text] [PDF]

				K. Thompson, J. Rojas-Navea, and M. J. Rogers Alkylamines cause V{gamma}9V{delta}2 T-cell activation and proliferation by inhibiting the mevalonate pathway Blood, January 15, 2006; 107(2): 651 - 654. [Abstract] [Full Text] [PDF]

				M. P. Jimenez de Bagues, A. Gross, A. Terraza, and J. Dornand Regulation of the Mitogen-Activated Protein Kinases by Brucella spp. Expressing a Smooth and Rough Phenotype: Relationship to Pathogen Invasiveness Infect. Immun., May 1, 2005; 73(5): 3178 - 3183. [Abstract] [Full Text] [PDF]

				B. Cipriani, H. Knowles, L. Chen, L. Battistini, and C. F. Brosnan Involvement of Classical and Novel Protein Kinase C Isoforms in the Response of Human V{gamma}9V{delta}2 T Cells to Phosphate Antigens J. Immunol., November 15, 2002; 169(10): 5761 - 5770. [Abstract] [Full Text] [PDF]

				E. Espinosa, J. Tabiasco, D. Hudrisier, and J.-J. Fournie Synaptic Transfer by Human {gamma}{delta} T Cells Stimulated with Soluble or Cellular Antigens J. Immunol., June 15, 2002; 168(12): 6336 - 6343. [Abstract] [Full Text] [PDF]