| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
,
Departments of
*
Pathology and
Medicine, and
Committee on Immunology, University of Chicago, Chicago, IL 60637
The formation of a conjugate between a T cell and an APC requires the activation of integrins on the T cell surface and remodeling of cytoskeletal elements at the cell-cell contact site via inside-out signaling. The early events in this signaling pathway are not well understood, and may differ from the events involved in adhesion to immobilized ligands. We find that conjugate formation between Jurkat T cells and EBV-B cells presenting superantigen is mediated by LFA-1 and absolutely requires Lck. Mutations in the Lck kinase, Src homology 2 or 3 domains, or the myristoylation site all inhibit conjugation to background levels, and adhesion cannot be restored by the expression of Fyn. However, ZAP-70-deficient cells conjugate normally, indicating that Lck is required for LFA-1-dependent adhesion via other downstream pathways. Several drugs that inhibit T cell adhesion to ICAM-1 immobilized on plastic, including inhibitors of mitogen-activated protein/extracellular signal-related kinase kinase, phosphatidylinositol-3 kinase, and calpain, do not inhibit conjugation. Inhibitors of phospholipase C and protein kinase C block conjugation of both wild-type and ZAP-70-deficient cells, suggesting that a phospholipase C that does not depend on ZAP-70 for its activation is involved. These results are not restricted to Jurkat T cells; Ag-specific primary T cell blasts behave similarly. Although the way in which Lck signals to enhance LFA-1-dependent adhesion is not clear, we find that cells lacking functional Lck fail to recruit F-actin and LFA-1 to the T cell:APC contact site, whereas ZAP-70-deficient cells show a milder phenotype characterized by disorganized actin and LFA-1 at the contact site.
This article has been cited by other articles:
|
|
 |
|
  W. Paster, C. Paar, P. Eckerstorfer, A. Jakober, K. Drbal, G. J. Schutz, A. Sonnleitner, and H. Stockinger Genetically Encoded Forster Resonance Energy Transfer Sensors for the Conformation of the Src Family Kinase Lck J. Immunol., February 15, 2009; 182(4): 2160 - 2167. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. Anton, A. Batista, J. Millan, L. Andres-Delgado, R. Puertollano, I. Correas, and M. A. Alonso An essential role for the MAL protein in targeting Lck to the plasma membrane of human T lymphocytes J. Exp. Med., December 22, 2008; 205(13): 3201 - 3213. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Huang, E. O. Comiskey, R. S. Dupree, S. Li, A. J. Koleske, and J. K. Burkhardt The c-Abl tyrosine kinase regulates actin remodeling at the immune synapse Blood, July 1, 2008; 112(1): 111 - 119. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Munoz, M. Mittelbrunn, H. de la Fuente, M. Perez-Martinez, A. Garcia-Perez, A. Ariza-Veguillas, F. Malavasi, M. Zubiaur, F. Sanchez-Madrid, and J. Sancho Antigen-induced clustering of surface CD38 and recruitment of intracellular CD38 to the immunologic synapse Blood, April 1, 2008; 111(7): 3653 - 3664. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Li, B. Ge, M. Nicotra, J. N. H. Stern, H. D. Kopcow, X. Chen, and J. L. Strominger JNK MAP kinase activation is required for MTOC and granule polarization in NKG2D-mediated NK cell cytotoxicity PNAS, February 26, 2008; 105(8): 3017 - 3022. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Alcazar, M. Marques, A. Kumar, E. Hirsch, M. Wymann, A. C. Carrera, and D. F. Barber Phosphoinositide 3 kinase {gamma} participates in T cell receptor induced T cell activation J. Exp. Med., November 26, 2007; 204(12): 2977 - 2987. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. L. Mueller, M. S. Thomas, B. J. Burbach, E. J. Peterson, and Y. Shimizu Adhesion and Degranulation-Promoting Adapter Protein (ADAP) Positively Regulates T Cell Sensitivity to Antigen and T Cell Survival J. Immunol., September 15, 2007; 179(6): 3559 - 3569. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. C. Nolz, R. B. Medeiros, J. S. Mitchell, P. Zhu, B. D. Freedman, Y. Shimizu, and D. D. Billadeau WAVE2 Regulates High-Affinity Integrin Binding by Recruiting Vinculin and Talin to the Immunological Synapse Mol. Cell. Biol., September 1, 2007; 27(17): 5986 - 6000. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. C. Nolz, M. E. Fernandez-Zapico, and D. D. Billadeau TCR/CD28-Stimulated Actin Dynamics Are Required for NFAT1-Mediated Transcription of c-rel Leading to CD28 Response Element Activation J. Immunol., July 15, 2007; 179(2): 1104 - 1112. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Castriconi, A. Dondero, C. Cantoni, M. Della Chiesa, C. Prato, M. Nanni, M. Fiorini, L. Notarangelo, S. Parolini, L. Moretta, et al. Functional characterization of natural killer cells in type I leukocyte adhesion deficiency Blood, June 1, 2007; 109(11): 4873 - 4881. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. T. N. Simonson, S. J. Franco, and A. Huttenlocher Talin1 Regulates TCR-Mediated LFA-1 Function J. Immunol., December 1, 2006; 177(11): 7707 - 7714. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. L. Rudd, A. Tua-Smith, and D. B. Straus Lck SH3 Domain Function Is Required for T-Cell Receptor Signals Regulating Thymocyte Development Mol. Cell. Biol., November 1, 2006; 26(21): 7892 - 7900. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Koneru, N. Monu, D. Schaer, J. Barletta, and A. B. Frey Defective Adhesion in Tumor Infiltrating CD8+ T Cells J. Immunol., May 15, 2006; 176(10): 6103 - 6111. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M.-C. Moldovan, L. Sabbagh, G. Breton, R.-P. Sekaly, and M. F. Krummel Triggering of T Cell Activation via CD4 Dimers J. Immunol., May 1, 2006; 176(9): 5438 - 5445. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. B. Martin-Cofreces, D. Sancho, E. Fernandez, M. Vicente-Manzanares, M. Gordon-Alonso, M. C. Montoya, F. Michel, O. Acuto, B. Alarcon, and F. Sanchez-Madrid Role of Fyn in the Rearrangement of Tubulin Cytoskeleton Induced through TCR J. Immunol., April 1, 2006; 176(7): 4201 - 4207. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Huang, D. D. Norton, P. Precht, J. L. Martindale, J. K. Burkhardt, and R. L. Wange Deficiency of ADAP/Fyb/SLAP-130 Destabilizes SKAP55 in Jurkat T Cells J. Biol. Chem., June 24, 2005; 280(25): 23576 - 23583. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Geyeregger, M. Zeyda, G. J. Zlabinger, W. Waldhausl, and T. M. Stulnig Polyunsaturated fatty acids interfere with formation of the immunological synapse J. Leukoc. Biol., May 1, 2005; 77(5): 680 - 688. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Koneru, D. Schaer, N. Monu, A. Ayala, and A. B. Frey Defective Proximal TCR Signaling Inhibits CD8+ Tumor-Infiltrating Lymphocyte Lytic Function J. Immunol., February 15, 2005; 174(4): 1830 - 1840. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. L. Mueller, M. A. Daniels, A. Felthauser, C. Kao, S. C. Jameson, and Y. Shimizu Cutting Edge: LFA-1 Integrin-Dependent T Cell Adhesion Is Regulated by Both Ag Specificity and Sensitivity J. Immunol., August 15, 2004; 173(4): 2222 - 2226. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. D. Perez, D. Mitchell, G. C. Jager, and G. P. Nolan LFA-1 signaling through p44/42 is coupled to perforin degranulation in CD56+CD8+ natural killer cells Blood, August 15, 2004; 104(4): 1083 - 1093. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. P. O'Keefe, K. Blaine, M.-L. Alegre, and T. F. Gajewski Formation of a central supramolecular activation cluster is not required for activation of naive CD8+ T cells PNAS, June 22, 2004; 101(25): 9351 - 9356. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. V. Rivas, J. P. O'Keefe, M.-L. Alegre, and T. F. Gajewski Actin Cytoskeleton Regulates Calcium Dynamics and NFAT Nuclear Duration Mol. Cell. Biol., February 15, 2004; 24(4): 1628 - 1639. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Wang, R. Matsumoto, Y. You, T. Che, X.-Y. Lin, S. L. Gaffen, and X. Lin CD3/CD28 Costimulation-Induced NF-{kappa}B Activation Is Mediated by Recruitment of Protein Kinase C-{theta}, Bcl10, and I{kappa}B Kinase {beta} to the Immunological Synapse through CARMA1 Mol. Cell. Biol., January 1, 2004; 24(1): 164 - 171. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Criado and J. Madrenas Superantigen Stimulation Reveals the Contribution of Lck to Negative Regulation of T Cell Activation J. Immunol., January 1, 2004; 172(1): 222 - 230. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Arp, M. G. Kirchhof, M. L. Baroja, S. H. Nazarian, T. A. Chau, C. A. Strathdee, E. H. Ball, and J. Madrenas Regulation of T-Cell Activation by Phosphodiesterase 4B2 Requires Its Dynamic Redistribution during Immunological Synapse Formation Mol. Cell. Biol., November 15, 2003; 23(22): 8042 - 8057. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. M. Hur, M. Son, O.-H. Lee, Y. B. Choi, C. Park, H. Lee, and Y. Yun LIME, a Novel Transmembrane Adaptor Protein, Associates with p56lck and Mediates T Cell Activation J. Exp. Med., November 10, 2003; (2003) 20030232. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Zeng, J. L. Cannon, R. T. Abraham, M. Way, D. D. Billadeau, J. Bubeck-Wardenberg, and J. K. Burkhardt SLP-76 Coordinates Nck-Dependent Wiskott-Aldrich Syndrome Protein Recruitment with Vav-1/Cdc42-Dependent Wiskott-Aldrich Syndrome Protein Activation at the T Cell-APC Contact Site J. Immunol., August 1, 2003; 171(3): 1360 - 1368. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M.-A. Langlois, Y. E. Fakhry, and W. Mourad Zinc-binding Sites in the N Terminus of Mycoplasma arthritidis-derived Mitogen Permit the Dimer Formation Required for High Affinity Binding to HLA-DR and for T Cell Activation J. Biol. Chem., June 13, 2003; 278(25): 22309 - 22315. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Sancho, M. C. Montoya, A. Monjas, M. Gordon-Alonso, T. Katagiri, D. Gil, R. Tejedor, B. Alarcon, and F. Sanchez-Madrid TCR Engagement Induces Proline-Rich Tyrosine Kinase-2 (Pyk2) Translocation to the T Cell-APC Interface Independently of Pyk2 Activity and in an Immunoreceptor Tyrosine-Based Activation Motif-Mediated Fashion J. Immunol., July 1, 2002; 169(1): 292 - 300. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
