| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
|
FJ
EXPRESS SUMMARY ARTICLE The Full-length version of this article is also available, published online July 24, 2000 as doi:10.1096/fj.99-0909fje. |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
T cells 1
* INSERM U395, CHU Purpan, BP3028, 31024 Toulouse, France;
INSERM U463, Institut de Biologie, 44035 Nantes France;
GICS, University of Georgetown, Washington, D.C., USA;
§ Sang Stat Medical Corporation, Menlo Park, California, USA; and
¶ Innate Pharma, chemin de Cassis, no. 121, 13009, Marseille, France
3Correspondence: fournie@purpan.inserm.fr
SPECIFIC AIMS
Human 
T lymphocytes
activate their immune function upon TCR-mediated recognition of
antigens not associated with MHC molecules. Because different
nonpeptide phosphorylated antigens (phosphoantigens) are selectively
recognized by T cells, we clarified its molecular basis through
the structure–function relationship of novel synthetic
phosphoantigens.
PRINCIPAL FINDINGS
Paradoxically, human T cell-mediated recognition of
phosphoantigens is highly specific and broadly cross-reactive. The
relationship between structure and activity of several natural or synthetic phosphoantigens shows the importance of conformational
determinants, but also reveals the critical role of the chemical
reactivity of phosphoantigens. Phosphoepoxides and
phosphohalohydrins are new synthetic phosphoantigens that were
designed on this basis and constitute the most potent
cell-stimulating compounds so far. For optimal V9V2 T cell
activation, both organic and phosphorylated moieties of these ligands
undergo rapid and degradative chemical changes such as
dephosphorylation. This irreversible phosphoantigen
consumption is rapid, cell-mediated, and may only be evidenced with
compounds bioactive in the nanomolar but not micromolar range.
Furthermore, whereas the structure of phosphoantigens is changed
upon their recognition by T cells, conversely, chemically
resistant phosphoantigen analogs antagonize phosphoantigen-mediated
T cell activation.FIGURE 1
FIGURE 2
|
|
CONCLUSIONS AND SIGNIFICANCE
These observations reveal a novel mode of antigenic recognition by
T cells, associating topological fit with chemical degradation of the
phosphoantigens. This explains why phosphoantigens cannot be stably
pulsed on presenting cells for recognition and how highly selective but
cross-reactive recognition of nonpeptide ligands may occur
simultaneously.FIGURE 3
|
FOOTNOTES
1 A study dedicated to the memory of Claude de Préval. 
2 Both of these authors contributed equally to this work.
To read the full text of this article, go to http://www.fasebj.org/cgi/doi/10.1096/fj.99-0909fje
This article has been cited by other articles:
|
|
 |
|
  H. Sicard, S. Ingoure, B. Luciani, C. Serraz, J.-J. Fournie, M. Bonneville, J. Tiollier, and F. Romagne In Vivo Immunomanipulation of V{gamma}9V{delta}2 T Cells with a Synthetic Phosphoantigen in a Preclinical Nonhuman Primate Model J. Immunol., October 15, 2005; 175(8): 5471 - 5480. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Corvaisier, A. Moreau-Aubry, E. Diez, J. Bennouna, J.-F. Mosnier, E. Scotet, M. Bonneville, and F. Jotereau V{gamma}9V{delta}2 T Cell Response to Colon Carcinoma Cells J. Immunol., October 15, 2005; 175(8): 5481 - 5488. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Rincon-Orozco, V. Kunzmann, P. Wrobel, D. Kabelitz, A. Steinle, and T. Herrmann Activation of V{gamma}9V{delta}2 T Cells by NKG2D J. Immunol., August 15, 2005; 175(4): 2144 - 2151. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Kato, Y. Tanaka, H. Tanaka, S. Yamashita, and N. Minato Requirement of Species-Specific Interactions for the Activation of Human {gamma}{delta} T Cells by Pamidronate J. Immunol., April 1, 2003; 170(7): 3608 - 3613. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. E. Rojas, M. Torres, J.-J. Fournie, C. V. Harding, and W. H. Boom Phosphoantigen Presentation by Macrophages to Mycobacterium tuberculosis-Reactive V{gamma}9V{delta}2+ T Cells: Modulation by Chloroquine Infect. Immun., August 1, 2002; 70(8): 4019 - 4027. [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]
|
|
|
|
|
|
C. Gioia, C. Agrati, R. Casetti, C. Cairo, G. Borsellino, L. Battistini, G. Mancino, D. Goletti, V. Colizzi, L. P. Pucillo, et al. Lack of CD27-CD45RA-V{gamma}9V{delta}2+ T Cell Effectors in Immunocompromised Hosts and During Active Pulmonary Tuberculosis J. Immunol., February 1, 2002; 168(3): 1484 - 1489. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Miyagawa, Y. Tanaka, S. Yamashita, B. Mikami, K. Danno, M. Uehara, and N. Minato Essential Contribution of Germline-Encoded Lysine Residues in J{gamma}1.2 Segment to the Recognition of Nonpeptide Antigens by Human {gamma}{delta} T Cells J. Immunol., December 15, 2001; 167(12): 6773 - 6779. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Kato, Y. Tanaka, F. Miyagawa, S. Yamashita, and N. Minato Targeting of Tumor Cells for Human {gamma}{delta} T Cells by Nonpeptide Antigens J. Immunol., November 1, 2001; 167(9): 5092 - 5098. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. T. Morita, H. K. Lee, H. Wang, H. Li, R. A. Mariuzza, and Y. Tanaka Structural Features of Nonpeptide Prenyl Pyrophosphates That Determine Their Antigenicity for Human {{gamma}}{{delta}} T Cells J. Immunol., July 1, 2001; 167(1): 36 - 41. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Miyagawa, Y. Tanaka, S. Yamashita, and N. Minato Essential Requirement of Antigen Presentation by Monocyte Lineage Cells for the Activation of Primary Human {{gamma}}{{delta}} T Cells by Aminobisphosphonate Antigen J. Immunol., May 1, 2001; 166(9): 5508 - 5514. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Altincicek, J. Moll, N. Campos, G. Foerster, E. Beck, J.-F. Hoeffler, C. Grosdemange-Billiard, M. Rodriguez-Concepcion, M. Rohmer, A. Boronat, et al. Cutting Edge: Human {{gamma}}{{delta}} T Cells Are Activated by Intermediates of the 2-C-methyl-D-erythritol 4-phosphate Pathway of Isoprenoid Biosynthesis J. Immunol., March 15, 2001; 166(6): 3655 - 3658. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Espinosa, C. Belmant, F. Pont, B. Luciani, R. Poupot, F. Romagne, H. Brailly, M. Bonneville, and J.-J. Fournie Chemical Synthesis and Biological Activity of Bromohydrin Pyrophosphate, a Potent Stimulator of Human gamma delta T Cells J. Biol. Chem., May 18, 2001; 276(21): 18337 - 18344. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
