| Autor: |
Smulski, C. (Cristian) R. (R), Beyrath, J. (Julien), Decossas, M. (Marion), Chekkat, N. (Neïla), Wolff, P. (Philippe), Estieu-Gionnet, K. (Karine), Guichard, G. (Gilles), Speiser, D. (Daniel), Schneider, P. (Pascal), Fournel, S. (Sylvie) |
| Jazyk: |
angličtina |
| Rok vydání: |
2013 |
| Předmět: |
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| Popis: |
The activation of CD40 on B cells, macrophages and dendritic cells by its ligand CD154 (CD40L) is essential for the development of humoral and cellular immune responses. CD40L and other TNF superfamily ligands are non-covalent homotrimers, but the form under which CD40 exists in the absence of ligand remains to be elucidated. Here we show that both cell surface-expressed and soluble CD40 self-assemble, most probably as non-covalent dimers. The cysteine-rich domain 1 (CRD1) of CD40 participated to dimerization and was also required for efficient receptor expression. Modelization of a CD40 dimer allowed the identification of lysine 29 in CRD1, whose mutation decreased CD40 self-interaction without affecting expression or response to ligand. When expressed alone, recombinant CD40-CRD1 bound CD40 with a KD of 0.6 µM. This molecule triggered expression of maturation markers on human dendritic cells and potentiated CD40L activity. These results suggest that CD40 self-assembly modulates signalling, possibly by maintaining the receptor in a quiescent state. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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