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Title
Japanese: 
English:Spatiotemporal Basis of CTLA-4 Costimulatory Molecule-Mediated Negative Regulation of T Cell Activation 
Author
Japanese: Tadashi Yokosuka, Wakana Kobayashi, Masako Takamatsu, 十川 久美子, Hu Zeng, Akiko Hashimoto-Tane, Hideo Yagita, 徳永 万喜洋, Takashi Saito.  
English: Tadashi Yokosuka, Wakana Kobayashi, Masako Takamatsu, Kumiko Sakata-Sogawa, Hu Zeng, Akiko Hashimoto-Tane, Hideo Yagita, Makio Tokunaga, Takashi Saito.  
Language English 
Journal/Book name
Japanese: 
English:Immunity 
Volume, Number, Page Vol. 33        pp. 326-339
Published date Sept. 2010 
Publisher
Japanese: 
English: 
Conference name
Japanese: 
English: 
Conference site
Japanese: 
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DOI https://doi.org/10.1016/j.immuni.2010.09.006
Abstract T cell activation is positively and negatively regulated by a pair of costimulatory receptors, CD28 and CTLA-4, respectively. Because these receptors share common ligands, CD80 and CD86, the expression and behavior of CTLA-4 is critical for T cell costimulation regulation. However, in vivo blocking of CD28-mediated costimulation by CTLA-4 and its mechanisms still remain elusive. Here, we demonstrate the dynamic behavior of CTLA-4 in its realtime competition with CD28 at the central-supramolecular activation cluster (cSMAC), resulting in the dislocalization of protein kinase C-θ and CARMA1 scaffolding protein. CTLA-4 translocation to the T cell receptor microclusters and the cSMAC is tightly regulated by its ectodomain size, and its accumulation at the cSMAC is required for its inhibitory function. The CTLA-4-mediated suppression was demonstrated by the in vitro anergy induction in regulatory T cells constitutively expressing CTLA-4. These results show the dynamic mechanism of CTLA-4-mediated T cell suppression at the cSMAC.

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