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

This Article Full Text Full Text (PDF, 465K) 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 CrossRef Citing Articles via Google Scholar Google Scholar Articles by Sahuquillo, A. G. Articles by Alarcón, B. Search for Related Content PubMed PubMed Citation Articles by Sahuquillo, A. G. Articles by Alarcón, B. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Social Bookmarking                            What's this?

Articles

T Cell Receptor (TCR) Engagement in Apoptosis-defective, but Interleukin 2 (IL-2)–producing, T Cells Results in Impaired ZAP70/CD3- Association

Almudena G. Sahuquillo^*, Anne Roumier, Emma Teixeiro, Rafael Bragado^*, and Balbino Alarcón

From the ^* Department of Immunology, Fundación Jiménez-Díaz, Avenida Reyes Católicos 2, 28040 Madrid, Spain; Departamento de Bioquímica y Biologia Molecular I, Universidad Complutense de Madrid, Spain; and Centro de Biología Molecular Severo Ochoa, CSIC-Universidad Autónoma de Madrid, Cantoblanco, 28049 Madrid, Spain

We have previously shown that a tyrosine to leucine replacement in the transmembrane region of T cell receptor (TCR)-β results in a deficient induction of CD95-L and apoptosis upon TCR triggering in a transfected T cell line. By contrast, interleukin (IL)-2 production and the expression of CD25 and CD69 were normally induced. Since the mutation in TCR-β also resulted in impaired association of CD3-, it was proposed that this chain is specifically required for the induction of apoptosis. We now show that the deficient induction of CD95-L and apoptosis does not derive from a general lower production of second messengers, since intracellular Ca²⁺ fluxes and tyrosine phosphorylation of total proteins were elicited at wild-type levels. Unlike in T cell clones stimulated with partial agonists, both p21 and p18 forms of tyrosine-phosphorylated CD3- were detected, although the overall level of tyrosine-phosphorylated CD3- was low. More strikingly, inducible association of ZAP70 to CD3- was strongly inhibited, despite a normal induction of ZAP70 tyrosine phosphorylation. Finally, ZAP70 was not concentrated near the plasma membrane in the apoptosis-deficient cells. These results suggest that CD3- is necessary for engagement of a specific signaling pathway leading to CD95-L expression that also needs the recruitment of ZAP70.

¹ Abbreviations used in this paper: APL, altered peptide ligands; ECL, enhanced chemiluminescence; GFP, green fluorescent protein; ITAM, immunoreceptor tyrosine-based activation motif; NFAT, nuclear factor of activated T cells; SEB, Staphylococcal enterotoxin B; SH2, src homology 2.

The first two authors contributed equally to this work.

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

Home | Help | Feedback | Subscriptions | Archive | Search

TABLE OF CONTENTS