Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text Full Text (PDF, 130K) PPT slides of all figures Alert me when this article is cited Citation Map Services Email this article Similar articles in this journal Similar articles in PubMed Alert me to new content in the JEM Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Viola, A. Articles by Lanzavecchia, A. Search for Related Content PubMed PubMed Citation Articles by Viola, A. Articles by Lanzavecchia, A. Social Bookmarking                            What's this?

Brief Definitive Reports

Antonella Viola^*, Mariolina Salio^*, Loretta Tuosto, Susanne Linkert^*, Oreste Acuto, and Antonio Lanzavecchia^*

From the ^* Basel Institute for Immunology, 4005, Basel, Switzerland; and Molecular Immunology Unit Institut Pasteur, 75724 Paris Cedex 15, France

CD4 and CD8 are thought to function as coreceptors by binding to the cognate major histocompatibility complex (MHC) molecules recognized by the T cell antigen receptor (TCR) and initiating the signal transduction cascade. We report that during T cell–antigen-presenting cell interaction, triggered TCRs and coreceptors are downregulated and degraded with identical kinetics. This coordinated disappearance takes place whenever the TCR is triggered, even when the coreceptor does not engage the cognate MHC molecule and is the consequence of binding of the coreceptor-associated Lck to ZAP-70. The interaction of coreceptor and cognate MHC molecules is dispensable when T cells are stimulated by optimal ligands, but becomes crucial when suboptimal ligands are used. In the latter case the coreceptor increases the efficiency of TCR triggering without changing the activation threshold or the quality of the T cell response.

The Basel Institute for Immunology was founded and is supported by F. Hoffmann La Roche Ltd., Basel, Switzerland.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

• Machlenkin, A., Uzana, R., Frankenburg, S., Eisenberg, G., Eisenbach, L., Pitcovski, J., Gorodetsky, R., Nissan, A., Peretz, T., Lotem, M. (2008). Capture of Tumor Cell Membranes by Trogocytosis Facilitates Detection and Isolation of Tumor-Specific Functional CTLs. Cancer Res. 68: 2006-2013 [Abstract] [Full Text]  
• Laugel, B., van den Berg, H. A., Gostick, E., Cole, D. K., Wooldridge, L., Boulter, J., Milicic, A., Price, D. A., Sewell, A. K. (2007). Different T Cell Receptor Affinity Thresholds and CD8 Coreceptor Dependence Govern Cytotoxic T Lymphocyte Activation and Tetramer Binding Properties. J. Biol. Chem. 282: 23799-23810 [Abstract] [Full Text]  
• Thedrez, A., de Lalla, C., Allain, S., Zaccagnino, L., Sidobre, S., Garavaglia, C., Borsellino, G., Dellabona, P., Bonneville, M., Scotet, E., Casorati, G. (2007). CD4 engagement by CD1d potentiates activation of CD4+ invariant NKT cells. Blood 110: 251-258 [Abstract] [Full Text]  
• Kienzle, N., Olver, S., Buttigieg, K., Groves, P., Janas, M. L., Baz, A., Kelso, A. (2005). Progressive Differentiation and Commitment of CD8+ T Cells to a Poorly Cytolytic CD8low Phenotype in the Presence of IL-4. J. Immunol. 174: 2021-2029 [Abstract] [Full Text]  
• Tavano, R., Gri, G., Molon, B., Marinari, B., Rudd, C. E., Tuosto, L., Viola, A. (2004). CD28 and Lipid Rafts Coordinate Recruitment of Lck to the Immunological Synapse of Human T Lymphocytes. J. Immunol. 173: 5392-5397 [Abstract] [Full Text]  
• Badran, B. M., Wolinsky, S. M., Burny, A., Willard-Gallo, K. E. (2002). Identification of Three NFAT Binding Motifs in the 5'-Upstream Region of the Human CD3gamma Gene That Differentially Bind NFATc1, NFATc2, and NF-kappa B p50. J. Biol. Chem. 277: 47136-47148 [Abstract] [Full Text]  
• Cawthon, A. G., Alexander-Miller, M. A. (2002). Optimal Colocalization of TCR and CD8 as a Novel Mechanism for the Control of Functional Avidity. J. Immunol. 169: 3492-3498 [Abstract] [Full Text]  
• Tuosto, L., Marinari, B., Piccolella, E. (2002). CD4-Lck Through TCR and in the Absence of Vav Exchange Factor Induces Bax Increase and Mitochondrial Damage. J. Immunol. 168: 6106-6112 [Abstract] [Full Text]  
• Jager, E., Salter, R., Castelli, C., Hohn, H., Freitag, K., Karbach, J., Neukirch, C., Necker, A., Knuth, A., Maeurer, M. J. (2002). Impact of Antigen Presentation on TCR Modulation and Cytokine Release: Implications for Detection and Sorting of Antigen-Specific CD8+ T Cells Using HLA-A2 Wild-Type or HLA-A2 Mutant Tetrameric Complexes. J. Immunol. 168: 2766-2772 [Abstract] [Full Text]  
• Utermohlen, O., Schulze-Garg, C., Warnecke, G., Gugel, R., Lohler, J., Deppert, W. (2001). Simian Virus 40 Large-T-Antigen-Specific Rejection of mKSA Tumor Cells in BALB/c Mice Is Critically Dependent on both Strictly Tumor-Associated, Tumor-Specific CD8+ Cytotoxic T Lymphocytes and CD4+ T Helper Cells. J. Virol. 75: 10593-10602 [Abstract] [Full Text]  
• Maile, R., Wang, B., Schooler, W., Meyer, A., Collins, E. J., Frelinger, J. A. (2001). Antigen-Specific Modulation of an Immune Response by In Vivo Administration of Soluble MHC Class I Tetramers. J. Immunol. 167: 3708-3714 [Abstract] [Full Text]  
• Diepolder, H. M., Gruener, N. H., Gerlach, J. T., Jung, M.-C., Wierenga, E. A., Pape, G. R. (2001). Different Levels of T-Cell Receptor Triggering Induce Distinct Functions in Hepatitis B and Hepatitis C Virus-Specific Human CD4+ T-Cell Clones. J. Virol. 75: 7803-7810 [Abstract] [Full Text]  
• Bryl, E., Gazda, M., Foerster, J., Witkowski, J. M. (2001). Age-related increase of frequency of a new, phenotypically distinct subpopulation of human peripheral blood T cells expressing lowered levels of CD4. Blood 98: 1100-1107 [Abstract] [Full Text]  
• Derby, M. A., Wang, J., Margulies, D. H., Berzofsky, J. A. (2001). Two intermediate-avidity cytotoxic T lymphocyte clones with a disparity between functional avidity and MHC tetramer staining. Int Immunol 13: 817-824 [Abstract] [Full Text]  
• Harder, T., Kuhn, M. (2000). Selective Accumulation of Raft-Associated Membrane Protein Lat in T Cell Receptor Signaling Assemblies. JCB 151: 199-208 [Abstract] [Full Text]  
• Lennon, G. P., Sillibourne, J. E., Furrie, E., Doherty, M. J., Kay, R. A. (2000). Antigen Triggering Selectively Increases TCRBV Gene Transcription. J. Immunol. 165: 2020-2027 [Abstract] [Full Text]  
• Bagriacik, E. U., Klein, J. R. (2000). The Thyrotropin (Thyroid-Stimulating Hormone) Receptor Is Expressed on Murine Dendritic Cells and on a Subset of CD45RBhigh Lymph Node T Cells: Functional Role for Thyroid-Stimulating Hormone During Immune Activation. J. Immunol. 164: 6158-6165 [Abstract] [Full Text]  
• Wiegers, G. J., Stec, I. E. M., Klinkert, W. E. F., Reul, J. M. H. M. (2000). Glucocorticoids Regulate TCR-Induced Elevation of CD4: Functional Implications. J. Immunol. 164: 6213-6220 [Abstract] [Full Text]  
• Lechner, F., Wong, D. K.H., Dunbar, P. R., Chapman, R., Chung, R. T., Dohrenwend, P., Robbins, G., Phillips, R., Klenerman, P., Walker, B. D. (2000). Analysis of Successful Immune Responses in Persons Infected with Hepatitis C Virus. JEM 191: 1499-1512 [Abstract] [Full Text]  
• Rogers, P. R., Croft, M. (2000). CD28, Ox-40, LFA-1, and CD4 Modulation of Th1/Th2 Differentiation Is Directly Dependent on the Dose of Antigen. J. Immunol. 164: 2955-2963 [Abstract] [Full Text]  
• Casares, S., Zong, C. S., Radu, D. L., Miller, A., Bona, C. A., Brumeanu, T.-D. (1999). Antigen-Specific Signaling by a Soluble, Dimeric Peptide/Major Histocompatibility Complex Class II/Fc Chimera Leading to T Helper Cell Type 2 Differentiation. JEM 190: 543-554 [Abstract] [Full Text]  
• Couedel, C., Bodinier, M., Peyrat, M.-A., Bonneville, M., Davodeau, F., Lang, F. (1999). Selection and Long-Term Persistence of Reactive CTL Clones During an EBV Chronic Response Are Determined by Avidity, CD8 Variable Contribution Compensating for Differences in TCR Affinities. J. Immunol. 162: 6351-6358 [Abstract] [Full Text]  
• Vallejo, A. N., Brandes, J. C., Weyand, C. M., Goronzy, J. J. (1999). Modulation of CD28 Expression: Distinct Regulatory Pathways During Activation and Replicative Senescence. J. Immunol. 162: 6572-6579 [Abstract] [Full Text]  
• Bachmann, M. F., Gallimore, A., Linkert, S., Cerundolo, V., Lanzavecchia, A., Kopf, M., Viola, A. (1999). Developmental Regulation of Lck Targeting to the CD8 Coreceptor Controls Signaling in Naive and Memory T Cells. JEM 189: 1521-1530 [Abstract] [Full Text]  
• Itoh, Y., Hemmer, B., Martin, R., Germain, R. N. (1999). Serial TCR Engagement and Down-Modulation by Peptide:MHC Molecule Ligands: Relationship to the Quality of Individual TCR Signaling Events. J. Immunol. 162: 2073-2080 [Abstract] [Full Text]  
• Thatte, J., Qadri, A., Radu, C., Ward, E. S. (1999). Molecular Requirements for T Cell Recognition by a Major Histocompatibility Complex Class II-restricted T Cell Receptor: The Involvement of the Fourth Hypervariable Loop of the V{alpha} Domain. JEM 189: 509-520 [Abstract] [Full Text]  
• Viola, A., Schroeder, S., Sakakibara, Y., Lanzavecchia, A. (1999). T Lymphocyte Costimulation Mediated by Reorganization of Membrane Microdomains. Science 283: 680-682 [Abstract] [Full Text]  
• LANZAVECCHIA, A. (1999). Three Signals and a Master Switch in the Regulation of T-cell Immunity. Cold Spring Harb Symp Quant Biol 64: 253-258 [Abstract]  
• Mostaghel, E. A., Riberdy, J. M., Steeber, D. A., Doyle, C. (1998). Coreceptor-Independent T Cell Activation in Mice Expressing MHC Class II Molecules Mutated in the CD4 Binding Domain. J. Immunol. 161: 6559-6566 [Abstract] [Full Text]  
• Hamad, A. R. A., O'Herrin, S. M., Lebowitz, M. S., Srikrishnan, A., Bieler, J., Schneck, J., Pardoll, D. (1998). Potent T Cell Activation with Dimeric Peptide-Major Histocompatibility Complex Class II Ligand: The Role of CD4 Coreceptor. JEM 188: 1633-1640 [Abstract] [Full Text]  
• Leitenberg, D., Boutin, Y., Constant, S., Bottomly, K. (1998). CD4 Regulation of TCR Signaling and T Cell Differentiation Following Stimulation with Peptides of Different Affinities for the TCR. J. Immunol. 161: 1194-1203 [Abstract] [Full Text]  
• Tomita, K., Saijo, K., Yamasaki, S., Iida, T., Nakatsu, F., Arase, H., Ohno, H., Shirasawa, T., Kuriyama, T., O'Shea, J. J., Saito, T. (2001). Cytokine-independent Jak3 Activation upon T Cell Receptor (TCR) Stimulation through Direct Association of Jak3 and the TCR Complex. J. Biol. Chem. 276: 25378-25385 [Abstract] [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search

TABLE OF CONTENTS