Qualitative and quantitative contributions of the T cell receptor zeta chain to mature T cell apoptosis

doi:10.1084/jem.183.5.2109

This Article

	Full Text (PDF, 1069K)
	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 Combadiere, B.
	Articles by Lenardo, M. J.
	Search for Related Content

PubMed

	PubMed Citation
	Articles by Combadiere, B.
	Articles by Lenardo, M. J.


Social Bookmarking

	What's this?

ARTICLES

Qualitative and quantitative contributions of the T cell receptor zeta chain to mature T cell apoptosis

B Combadiere, M Freedman, L Chen, EW Shores, P Love and MJ Lenardo
Laboratory of Immunology, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.

Engagement of the T cell receptor (TCR) of mature T lymphocytes can lead either to activation/proliferation responses or programmed cell death. To understand the molecular regulation of these two fundamentally different outcomes of TCR signaling, we investigated the participation of various components of the TCR-CD3 complex. We found that the TCR-zeta chain, while not absolutely required, was especially effective at promoting mature T cell apoptosis compared with the CD3 epsilon, gamma, or delta chains. We also carried out mutagenesis to address the role of the immunoreceptor tyrosine-based activation motifs (ITAMs) that are the principal signaling components found three times in the TCR-zeta chain and once in each of the CD3 epsilon, gamma, or delta chains. We found that the ability of the TCR-zeta chain to promote apoptosis results both from a quantitative effect of the presence of multiple ITAMs as well as qualitatively different contributions made by individual ITAMs. Apoptosis induced by single chain chimeras revealed that the first zeta ITAM stimulated greater apoptosis than the third zeta ITAM, and the second zeta ITAM was unable to trigger apoptosis. Because microheterogeneity in the amino acid sequence of the various ITAM motifs found in the TCR-zeta and CD3 chains predicts interactions with distinct src-homology-2-domain signaling proteins, our results suggest the possibility that individual ITAM motifs might play unique roles in TCR responses by engaging specific signaling pathways.
Add to CiteULike CiteULike Add to Complore Complore Add to Connotea Connotea Add to Del.icio.us Del.icio.us Add to Digg Digg Facebook Add to Reddit Reddit Add to Technorati Technorati Twitter What's this?

This article has been cited by other articles:

Zhao, Y., Wang, Q. J., Yang, S., Kochenderfer, J. N., Zheng, Z., Zhong, X., Sadelain, M., Eshhar, Z., Rosenberg, S. A., Morgan, R. A. (2009). A Herceptin-Based Chimeric Antigen Receptor with Modified Signaling Domains Leads to Enhanced Survival of Transduced T Lymphocytes and Antitumor Activity. J. Immunol. 183: 5563-5574 [Abstract] [Full Text]
Zhang, Z., Gorman, C. L., Vermi, A.-C., Monaco, C., Foey, A., Owen, S., Amjadi, P., Vallance, A., McClinton, C., Marelli-Berg, F., Isomaki, P., Russell, A., Dazzi, F., Vyse, T. J., Brennan, F. M., Cope, A. P. (2007). TCR{zeta}dimlymphocytes define populations of circulating effector cells that migrate to inflamed tissues. Blood 109: 4328-4335 [Abstract] [Full Text]
Wang, S., Wang, S., Maeng, H., Young, D. P., Prakash, O., Fayad, L. E., Younes, A., Samaniego, F. (2007). K1 protein of human herpesvirus 8 suppresses lymphoma cell Fas-mediated apoptosis. Blood 109: 2174-2182 [Abstract] [Full Text]
Kanamaru, Y., Tamouza, H., Pfirsch, S., El Mehdi, D., Guerin-Marchand, C., Pretolani, M., Blank, U., Monteiro, R. C. (2007). IgA Fc receptor I signals apoptosis through the FcR{gamma} ITAM and affects tumor growth. Blood 109: 203-211 [Abstract] [Full Text]
Chae, W.-J., Lee, H.-K., Han, J.-H., Kim, S.-W. V., Bothwell, A. L.M., Morio, T., Lee, S.-K. (2004). Qualitatively differential regulation of T cell activation and apoptosis by T cell receptor {zeta} chain ITAMs and their tyrosine residues. Int Immunol 16: 1225-1236 [Abstract] [Full Text]
Siu, E., Carreno, B. M., Madrenas, J. (2003). TCR subunit specificity of CTLA-4-mediated signaling. J. Leukoc. Biol. 74: 1102-1107 [Abstract] [Full Text]
Uemura, Y., Senju, S., Maenaka, K., Iwai, L. K., Fujii, S., Tabata, H., Tsukamoto, H., Hirata, S., Chen, Y.-Z., Nishimura, Y. (2003). Systematic Analysis of the Combinatorial Nature of Epitopes Recognized by TCR Leads to Identification of Mimicry Epitopes for Glutamic Acid Decarboxylase 65-Specific TCRs. J. Immunol. 170: 947-960 [Abstract] [Full Text]
Haks, M. C., Pepin, E., van den Brakel, J. H.N., Smeele, S. A.A., Belkowski, S. M., Kessels, H. W.H.G., Krimpenfort, P., Kruisbeek, A. M. (2002). Contributions of the T Cell Receptor-associated CD3{gamma}-ITAM to Thymocyte Selection. JEM 196: 1-13 [Abstract] [Full Text]
Rodriguez, P. C., Zea, A. H., Culotta, K. S., Zabaleta, J., Ochoa, J. B., Ochoa, A. C. (2002). Regulation of T Cell Receptor CD3zeta Chain Expression by L-Arginine. J. Biol. Chem. 277: 21123-21129 [Abstract] [Full Text]
Teixeiro, E., Fuentes, P., Galocha, B., Alarcon, B., Bragado, R. (2002). T Cell Receptor-mediated Signal Transduction Controlled by the beta Chain Transmembrane Domain. APOPTOSIS-DEFICIENT CELLS DISPLAY UNBALANCED MITOGEN-ACTIVATED PROTEIN KINASES ACTIVITIES UPON T CELL RECEPTOR ENGAGEMENT. J. Biol. Chem. 277: 3993-4002 [Abstract] [Full Text]
Steff, A.-M., Trop, S., Maira, M., Drouin, J., Hugo, P. (2001). Opposite Ability of Pre-TCR and {{alpha}}{{beta}}TCR to Induce Apoptosis. J. Immunol. 166: 5044-5050 [Abstract] [Full Text]
Haks, M. C., Cordaro, T. A., van den Brakel, J. H. N., Haanen, J. B. A. G., de Vries, E. F. R., Borst, J., Krimpenfort, P., Kruisbeek, A. M. (2001). A Redundant Role of the CD3{{gamma}}-Immunoreceptor Tyrosine-Based Activation Motif in Mature T Cell Function. J. Immunol. 166: 2576-2588 [Abstract] [Full Text]
Kunjibettu, S., Fuller-Espie, S., Carey, G. B., Spain, L. M. (2001). Conserved transmembrane tyrosine residues of the TCR {beta} chain are required for TCR expression and function in primary T cells and hybridomas. Int Immunol 13: 211-222 [Abstract] [Full Text]
Kersh, E. N., Kersh, G. J., Allen, P. M. (1999). Partially Phosphorylated T Cell Receptor {zeta} Molecules Can Inhibit T Cell Activation. JEM 190: 1627-1636 [Abstract] [Full Text]
Xu, X.-N., Laffert, B., Screaton, G. R., Kraft, M., Wolf, D., Kolanus, W., Mongkolsapay, J., McMichael, A. J., Baur, A. S. (1999). Induction of Fas Ligand Expression by HIV Involves the Interaction of Nef with the T Cell Receptor {zeta} Chain. JEM 189: 1489-1496 [Abstract] [Full Text]
Kessler, B., Hudrisier, D., Schroeter, M., Tschopp, J., Cerottini, J.-C., Luescher, I. F. (1998). Peptide Modification or Blocking of CD8, Resulting in Weak TCR Signaling, Can Activate CTL for Fas- But Not Perforin-Dependent Cytotoxicity or Cytokine Production. J. Immunol. 161: 6939-6946 [Abstract] [Full Text]
Rivoltini, L., Radrizzani, M., Accornero, P., Squarcina, P., Chiodoni, C., Mazzocchi, A., Castelli, C., Tarsini, P., Viggiano, V., Belli, F., Colombo, M. P., Parmiani, G. (1998). Human Melanoma-Reactive CD4+ and CD8+ CTL Clones Resist Fas Ligand-Induced Apoptosis and Use Fas/Fas Ligand-Independent Mechanisms for Tumor Killing. J. Immunol. 161: 1220-1230 [Abstract] [Full Text]
Hudrisier, D., Kessler, B., Valitutti, S., Horvath, C., Cerottini, J.-C., Luescher, I. F. (1998). The Efficiency of Antigen Recognition by CD8+ CTL Clones Is Determined by the Frequency of Serial TCR Engagement. J. Immunol. 161: 553-562 [Abstract] [Full Text]
Roberts, M. R., Cooke, K. S., Tran, A.-C., Smith, K. A., Lin, W. Y., Wang, M., Dull, T. J., Farson, D., Zsebo, K. M., Finer, M. H. (1998). Antigen-Specific Cytolysis by Neutrophils and NK Cells Expressing Chimeric Immune Receptors Bearing {zeta} or {gamma} Signaling Domains. J. Immunol. 161: 375-384 [Abstract] [Full Text]
Sahuquillo, A. G., Roumier, A., Teixeiro, E., Bragado, R., Alarcon, B. (1998). T Cell Receptor (TCR) Engagement in Apoptosis-defective, but Interleukin 2 (IL-2)-producing, T Cells Results in Impaired ZAP70/CD3-{zeta} Association. JEM 187: 1179-1192 [Abstract] [Full Text]
Lowin-Kropf, B., Shapiro, V. S., Weiss, A. (1998). Cytoskeletal Polarization of T Cells Is Regulated by an Immunoreceptor Tyrosine-based Activation Motif-dependent Mechanism. JCB 140: 861-871 [Abstract] [Full Text]
van Oers, N. S. C., Love, P. E., Shores, E. W., Weiss, A. (1998). Regulation of TCR Signal Transduction in Murine Thymocytes by Multiple TCR {zeta}-Chain Signaling Motifs. J. Immunol. 160: 163-170 [Abstract] [Full Text]
Shores, E. W., Tran, T., Grinberg, A., Sommers, C. L., Shen, H., Love, P. E. (1997). Role of the Multiple T Cell Receptor (TCR)-{zeta} Chain Signaling Motifs in Selection of the T Cell Repertoire. JEM 185: 893-900 [Abstract] [Full Text]
Chen, T., Bolland, S., Chen, I., Parker, J., Pantelic, M., Grunert, F., Zimmermann, W. (2001). The CGM1a (CEACAM3/CD66d)-mediated Phagocytic Pathway of Neisseria gonorrhoeae Expressing Opacity Proteins Is Also the Pathway to Cell Death. J. Biol. Chem. 276: 17413-17419 [Abstract] [Full Text]