Essential Role of CD8 Palmitoylation in CD8 Coreceptor Function
| Autor: | Immanuel F. Luescher, Alexandre Arcaro, Bernard Malissen, Sabine H. Stotz, Ed Palmer, Nicole Boucheron, Claude Grégoire |
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| Rok vydání: | 2000 |
| Předmět: |
CD3 Complex
Plasmodium berghei CD8 Antigens T-Lymphocytes T cell Detergents Molecular Sequence Data Immunology Phosphatase Palmitic Acid Protozoan Proteins Receptors Antigen T-Cell Lymphocyte Activation Mice Palmitoylation medicine Animals Immunology and Allergy Amino Acid Sequence Phosphorylation Peptide sequence Lipid raft Hybridomas Chemistry H-2 Antigens hemic and immune systems Peptide Fragments Protein Structure Tertiary Cell biology Enzyme Activation medicine.anatomical_structure Biochemistry Lymphocyte Specific Protein Tyrosine Kinase p56(lck) Cytoplasm lipids (amino acids peptides and proteins) 4-Aminobenzoic Acid Proto-oncogene tyrosine-protein kinase Src |
| Zdroj: | The Journal of Immunology. 165:2068-2076 |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | To investigate the molecular basis that makes heterodimeric CD8αβ a more efficient coreceptor than homodimeric CD8αα, we used various CD8 transfectants of T1.4 T cell hybridomas, which are specific for H-2Kd, and a photoreactive derivative of the Plasmodium berghei circumsporozoite peptide PbCS 252–260 (SYIPSAEKI). We demonstrate that CD8 is palmitoylated at the cytoplasmic tail of CD8β and that this allows partitioning of CD8αβ, but not of CD8αα, in lipid rafts. Localization of CD8 in rafts is crucial for its coreceptor function. First, association of CD8 with the src kinase p56lck takes place nearly exclusively in rafts, mainly due to increased concentration of both components in this compartment. Deletion of the cytoplasmic domain of CD8β abrogated localization of CD8 in rafts and association with p56lck. Second, CD8-mediated cross-linking of p56lck by multimeric Kd-peptide complexes or by anti-CD8 Ab results in p56lck activation in rafts, from which the abundant phosphatase CD45 is excluded. Third, CD8-associated activated p56lck phosphorylates CD3ζ in rafts and hence induces TCR signaling and T cell activation. This study shows that palmitoylation of CD8β is required for efficient CD8 coreceptor function, mainly because it dramatically increases CD8 association with p56lck and CD8-mediated activation of p56lck in lipid rafts. |
| Databáze: | OpenAIRE |
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