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Proximal changes in signal transduction that modify CD8+ T cell responsiveness in vivo

✍ Scribed by Séverine Guillaume; Loretta Tuosto; Corinne Tanchot; Vincenzo Di Bartolo; Oreste Acuto; Benedita Rocha

Publisher
John Wiley and Sons
Year
2003
Tongue
English
Weight
169 KB
Volume
33
Category
Article
ISSN
0014-2980

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✦ Synopsis

Abstract

The antigen dose conditions the functional properties of CD8^+^ T cells generated after priming. At relatively low antigen doses, efficient memory T cells may be generated, while high antigen doses lead to tolerance. To determine the mechanisms leading to such different functional outcomes, we compared the proximal TCR signal transduction of naive cells, to that of memory or high‐dose tolerant cells generated in vivo. In vivo activation led to the constitutive phosphorylation of CD3ϵ, recruiting Zap70, in both memory and tolerant cells. In tolerant cells, these phenomena were much more marked, the CD3ϵ and ζ chains no longer associated, and the Src kinases p56Lck and p59Fyn were inactive. Therefore, when the antigen load overcomes the capacities of immune control, a new mechanism intervenes to block signal transduction: the recruitment of Zap70 to CD3ϵ becomes excessive, leading to TCR complex destabilization, Src kinase dysfunction, and signal arrest.

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