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Blood, 15 January 2006, Vol. 107, No. 2, pp. 651-654. Prepublished online as a Blood First Edition Paper on September 22, 2005; DOI 10.1182/blood-2005-03-1025. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: 2005-03-1025v1 107/2/651    most recent 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 Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Thompson, K. Articles by Rogers, M. J. Search for Related Content PubMed PubMed Citation Articles by Thompson, K. Articles by Rogers, M. J. Related Collections Immunobiology Signal Transduction Brief Reports Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Brief report Alkylamines cause V9V2 T-cell activation and proliferation by inhibiting the mevalonate pathway Keith Thompson, Javier Rojas-Navea, and Michael J. Rogers From the Bone Research Group, University of Aberdeen, Institute of Medical Sciences, Foresterhill, Aberdeen, United Kingdom. Three general classes of small, nonpeptide "antigens" activate V9V2 T cells: pyrophosphomonoesters, such as isopentenyl diphosphate (IPP), nitrogen-containing bisphosphonates (N-BPs), and alkylamines. However, we have shown recently that N-BPs indirectly activate V9V2 T cells as a consequence of inhibition of farnesyl diphosphate synthase (a key enzyme of the mevalonate pathway) and the intracellular accumulation of IPP. We now show that alkylamines activate V9V2 T cells by the same mechanism. Alkylamines were found to be weak inhibitors of farnesyl diphosphate synthase and caused accumulation of unprenylated Rap1A in peripheral blood mononuclear cells and macrophages, indicative of inhibition of the mevalonate pathway. Furthermore, as with N-BPs, the stimulatory effect of the alkylamines on V9V2T cells was abrogated by simultaneous treatment with mevastatin. These findings suggest that only pyrophosphomonoesters such as IPP are true V9V2 T-cell agonists, whereas alkylamines and N-BPs indirectly activate V9V2 T cells through a common mechanism involving the accumulation of IPP. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. Li, M. J. Herold, B. Kimmel, I. Muller, B. Rincon-Orozco, V. Kunzmann, and T. Herrmann Reduced Expression of the Mevalonate Pathway Enzyme Farnesyl Pyrophosphate Synthase Unveils Recognition of Tumor Cells by V{gamma}9V{delta}2 T Cells J. Immunol., June 15, 2009; 182(12): 8118 - 8124. [Abstract] [Full Text] [PDF] G. Sarikonda, H. Wang, K.-J. Puan, X.-h. Liu, H. K. Lee, Y. Song, M. D. Distefano, E. Oldfield, G. D. Prestwich, and C. T. Morita Photoaffinity Antigens for Human {gamma}{delta} T Cells J. Immunol., December 1, 2008; 181(11): 7738 - 7750. [Abstract] [Full Text] [PDF] J. Holderness, L. Jackiw, E. Kimmel, H. Kerns, M. Radke, J. F. Hedges, C. Petrie, P. McCurley, P. M. Glee, A. Palecanda, et al. Select Plant Tannins Induce IL-2R{alpha} Up-Regulation and Augment Cell Division in {gamma}{delta} T Cells J. Immunol., November 15, 2007; 179(10): 6468 - 6478. [Abstract] [Full Text] [PDF] K.-J. Puan, C. Jin, H. Wang, G. Sarikonda, A. M. Raker, H. K. Lee, M. I. Samuelson, E. Marker-Hermann, L. Pasa-Tolic, E. Nieves, et al. Preferential recognition of a microbial metabolite by human V{gamma}2V{delta}2 T cells Int. Immunol., May 1, 2007; 19(5): 657 - 673. [Abstract] [Full Text] [PDF] K. Thompson and M. J. Rogers Bisphosphonates and {gamma}{delta} T-Cells: New Insights into Old Drugs IBMS BoneKEy, August 1, 2006; 3(8): 5 - 13. [Abstract] [Full Text] [PDF] Y. Kato, Y. Tanaka, M. Hayashi, K. Okawa, and N. Minato Involvement of CD166 in the Activation of Human {gamma}{delta}T Cells by Tumor Cells Sensitized with Nonpeptide Antigens J. Immunol., July 15, 2006; 177(2): 877 - 884. [Abstract] [Full Text] [PDF]

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