Spatiotemporal basis of CTLA-4 costimulatory molecule-mediated negative regulation of T cell activation
| Autor: | Tadashi Yokosuka, Makio Tokunaga, Takashi Saito, Masako Takamatsu, Kumiko Sakata-Sogawa, Akiko Hashimoto-Tane, Hu Zeng, Hideo Yagita, Wakana Kobayashi |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
CD3 Complex
T cell T-Lymphocytes Immunology chemical and pharmacologic phenomena Biology Lymphocyte Activation T-Lymphocytes Regulatory Mice CD28 Antigens Antigens CD medicine Immune Tolerance Immunology and Allergy Animals CTLA-4 Antigen Protein kinase A Receptor Cells Cultured Protein Kinase C CD86 T-cell receptor CD28 hemic and immune systems biological factors Cell biology CARD Signaling Adaptor Proteins Isoenzymes medicine.anatomical_structure Infectious Diseases CTLA-4 Protein Kinase C-theta CD80 |
| Zdroj: | Immunity. 33(3) |
| ISSN: | 1097-4180 |
| Popis: | SummaryT 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 real-time 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. |
| Databáze: | OpenAIRE |
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