TCR activation kinetics and feedback regulation in primary human T cells

Cell Communication and Signaling

Research

Amarendra V Reddycherla¹  Jonathan A Lindquist¹  Luca Simeoni¹  Bhavani S Kowtharapu¹  Boerge Arndt¹  Vanessa Witte¹  Mateusz Poltorak¹  Burkhart Schraven¹ 

[1]Institute of Molecular and Clinical Immunology, Otto-von-Guericke University, Leipziger Str. 44, 39120, Magdeburg, Germany

关键词: TCR-mediated signaling;    Feedback regulation;    Cell-fate specification;    T-cell activation;    Lck;    Erk;    Signaling dynamics;    CD4 crosslinking;   

DOI  :  10.1186/1478-811X-11-4

 received in 2012-09-28, accepted in 2013-01-09,  发布年份 2013

来源: Springer

【 摘 要 】

BackgroundSignaling through the TCR is crucial for the generation of different cellular responses including proliferation, differentiation, and apoptosis. A growing body of evidence indicates that differences in the magnitude and the duration of the signal are critical determinants in eliciting cellular responses.ResultsHere, we have analyzed signaling dynamics correlating with either unresponsiveness or proliferation induced upon TCR/CD28 ligation in primary human T cells. We used two widely employed methods to stimulate T cells in vitro, antibodies either cross-linked in solution (sAbs) or immobilized on microbeads (iAbs). A comparative analysis of the signaling properties of iAbs and sAbs revealed that, under proliferation-inducing conditions, feedback regulation is markedly different from that leading to an unresponsive state. In fact, upon iAbs stimulation TCR-mediated signaling is prolonged by a positive feedback loop involving Erk, whereas sAbs strongly activate inhibitory molecules that likely terminate signaling. We additionally found that, by enhancing the phosphorylation of Src family kinases under proliferation-inducing conditions, signaling and T-cell activation are terminated.ConclusionsIn summary, our analysis documents TCR signaling kinetics and feedback regulation under conditions of stimulation inducing either unresponsiveness or proliferation.

【 授权许可】

Unknown   
© Poltorak et al.; licensee BioMed Central Ltd. 2013. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.