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Science 5 July 1996:
Vol. 273. no. 5271, pp. 104 - 106
DOI: 10.1126/science.273.5271.104
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Reports

T Cell Activation Determined by T Cell Receptor Number and Tunable Thresholds

Antonella Viola and Antonio Lanzavecchia *

The requirements for T cell activation have been reported to vary widely depending on the state of the T cell, the type of antigen-presenting cell, and the nature of the T cell receptor (TCR) ligand. A unitary requirement for T cell responses was revealed by measurement of the number of triggered TCRs. Irrespective of the nature of the triggering ligand, T cells "counted" the number of triggered TCRs and responded when a threshold of sim 8000 TCRs was reached. The capacity to reach the activation threshold was severely compromised by a reduction in the number of TCRs. Costimulatory signals lowered the activation threshold to sim 1500 TCRs, thus making T cells more sensitive to antigenic stimulation.

Basel Institute for Immunology, Grenzacherstrasse 487, CH 4005 Basel, Switzerland.
* To whom correspondence should be addressed. E-mail: Lanzavecchia{at}bii.ch


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J. Immunol. 169, 3581-3588
   Abstract »    Full Text »    PDF »
T Cells Primed by Leishmania major Infection Cross-React with Alloantigens and Alter the Course of Allograft Rejection.
B. Pantenburg, F. Heinzel, L. Das, P. S. Heeger, and A. Valujskikh (2002)
J. Immunol. 169, 3686-3693
   Abstract »    Full Text »    PDF »
The Proliferative Capacity of Individual Naive CD4+T Cells Is Amplified by Prolonged T Cell Antigen Receptor Triggering.
A. G. Schrum and L. A. Turka (2002)
J. Exp. Med. 196, 793-803
   Abstract »    Full Text »    PDF »
Cutting Edge: The Relative Distribution of T Cells Responding to Chemically Dominant or Minor Epitopes of Lysozyme Is Not Affected by CD40-CD40 Ligand and B7-CD28-CTLA-4 Costimulatory Pathways.
R. J. DiPaolo and E. R. Unanue (2002)
J. Immunol. 169, 2832-2836
   Abstract »    Full Text »    PDF »
Modulation of TCR-induced transcriptional profiles by ligation of CD28, ICOS, and CTLA-4 receptors.
J. L. Riley, M. Mao, S. Kobayashi, M. Biery, J. Burchard, G. Cavet, B. P. Gregson, C. H. June, and P. S. Linsley (2002)
PNAS 99, 11790-11795
   Abstract »    Full Text »    PDF »
Cutting Edge: Regulation of T Cell Activation Threshold by CD28 Costimulation Through Targeting Cbl-b for Ubiquitination.
J. Zhang, T. Bardos, D. Li, I. Gal, C. Vermes, J. Xu, K. Mikecz, A. Finnegan, S. Lipkowitz, and T. T. Glant (2002)
J. Immunol. 169, 2236-2240
   Abstract »    Full Text »    PDF »
A Panel of Candidate Tumor Antigens in Colorectal Cancer Revealed by the Serological Selection of a Phage Displayed cDNA Expression Library.
V. A. Somers, R. J. Brandwijk, B. Joosten, P. T. Moerkerk, J.-W. Arends, P. Menheere, W. O. Pieterse, A. Claessen, R. J. Scheper, H. R. Hoogenboom, et al. (2002)
J. Immunol. 169, 2772-2780
   Abstract »    Full Text »    PDF »
CD28 Costimulation: A Source of Vav-1 for TCR Signaling with the Help of SLP-76?.
F. Michel and O. Acuto (2002)
Sci. STKE 2002, pe35
   Abstract »    Full Text »    PDF »
Direct Ex Vivo Analysis of Human CD4+ Memory T Cell Activation Requirements at the Single Clonotype Level.
A. D. Bitmansour, D. C. Douek, V. C. Maino, and L. J. Picker (2002)
J. Immunol. 169, 1207-1218
   Abstract »    Full Text »    PDF »
A Role for Inducible Costimulator Protein in the CD28- Independent Mechanism of Resistance to Toxoplasma gondii.
E. N. Villegas, L. A. Lieberman, N. Mason, S. L. Blass, V. P. Zediak, R. Peach, T. Horan, S. Yoshinaga, and C. A. Hunter (2002)
J. Immunol. 169, 937-943
   Abstract »    Full Text »    PDF »
Serial Triggering of T Cell Receptors Results in Incremental Accumulation of Signaling Intermediates.
Z. Borovsky, G. Mishan-Eisenberg, E. Yaniv, and J. Rachmilewitz (2002)
J. Biol. Chem. 277, 21529-21536
   Abstract »    Full Text »    PDF »
Ligand-Induced TCR Down-Regulation Is Not Dependent on Constitutive TCR Cycling.
J. Dietrich, C. Menne, J. P. H. Lauritsen, M. von Essen, A. B. Rasmussen, N. Odum, and C. Geisler (2002)
J. Immunol. 168, 5434-5440
   Abstract »    Full Text »    PDF »
Differentiation of Human CD8+ T Cells from a Memory to Memory/Effector Phenotype.
H. Tomiyama, T. Matsuda, and M. Takiguchi (2002)
J. Immunol. 168, 5538-5550
   Abstract »    Full Text »    PDF »
B7-CTLA4 interaction promotes cognate destruction of tumor cells by cytotoxic T lymphocytes in vivo.
X.-F. Bai, J. Liu, K. F. May Jr, Y. Guo, P. Zheng, and Y. Liu (2002)
Blood 99, 2880-2889
   Abstract »    Full Text »    PDF »
Naive CD4+ T Cells Exhibit Distinct Expression Patterns of Cytokines and Cell Surface Molecules on Their Primary Responses to Varying Doses of Antigen.
W. Ise, M. Totsuka, Y. Sogawa, A. Ametani, S. Hachimura, T. Sato, Y. Kumagai, S. Habu, and S. Kaminogawa (2002)
J. Immunol. 168, 3242-3250
   Abstract »    Full Text »    PDF »
Rap1 Functions as a Key Regulator of T-Cell and Antigen-Presenting Cell Interactions and Modulates T-Cell Responses.
K. Katagiri, M. Hattori, N. Minato, and T. Kinashi (2002)
Mol. Cell. Biol. 22, 1001-1015
   Abstract »    Full Text »    PDF »
Pharmacokinetics of Murine Anti-Human CD3 Antibodies in Man Are Determined by the Disappearance of Target Antigen.
R. T. Meijer, R. P. Koopmans, I. J. M. ten Berge, and P. T. A. Schellekens (2002)
J. Pharmacol. Exp. Ther. 300, 346-353
   Abstract »    Full Text »    PDF »


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