CD80 and CD86 IgC domains are important for quaternary structure, receptor binding and co-signaling function
| Autor: | Tanya Girard, Gaëlle Breton, Mohamed El-Far, Denis Gaucher, Rafick-Pierre Sekaly |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
T cell
Immunology chemical and pharmacologic phenomena Lymphocyte Activation Cell Line CD28 Antigens Fluorescence Resonance Energy Transfer medicine Humans Immunology and Allergy CTLA-4 Antigen Protein Interaction Domains and Motifs Protein Structure Quaternary Receptor Sequence Deletion CD86 Chemistry Cell Membrane CD28 hemic and immune systems Flow Cytometry Molecular biology medicine.anatomical_structure B7-1 Antigen Biophysics Interleukin-2 Protein quaternary structure B7-2 Antigen Protein Multimerization Intracellular Function (biology) CD80 Protein Binding Signal Transduction |
| Zdroj: | Immunology Letters. 161:65-75 |
| ISSN: | 0165-2478 |
| DOI: | 10.1016/j.imlet.2014.05.002 |
| Popis: | CD86 and CD80, the ligands for the co-stimulatory molecules CD28 and CTLA-4, are members of the Ig superfamily. Their structure includes Ig variable-like (IgV) domains, Ig constant-like (IgC) domains and intracellular domains. Although crystallographic studies have clearly identified the IgV domain to be responsible for receptor interactions, earlier studies suggested that both Ig domains are required for full co-signaling function. Herein, we have used deletion and chimeric human CD80 and CD86 molecules in co-stimulation assays to study the impact of the multimeric state of IgV and IgC domains on receptor binding properties and on co-stimulatory function in a peptide-specific T cell activation model. We report for the first time the presence of CD80 dimers and CD86 monomers in living cells. Moreover, we show that the IgC domain of both molecules inhibits multimer formation and greatly affects binding to the co-receptors CD28 and CTLA-4. Finally, both IgC and intracellular domains are required for full co-signaling function. These findings reveal the distinct but complementary roles of CD80 and CD86 IgV and IgC domains in T cell activation. |
| Databáze: | OpenAIRE |
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