Essential role of CD8 palmitoylation in CD8 coreceptor function.

Details

Serval ID
serval:BIB_0E87416503C7
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Essential role of CD8 palmitoylation in CD8 coreceptor function.
Journal
Journal of immunology
Author(s)
Arcaro A., Grégoire C., Boucheron N., Stotz S., Palmer E., Malissen B., Luescher I.F.
ISSN
0022-1767
Publication state
Published
Issued date
2000
Peer-reviewed
Oui
Volume
165
Number
4
Pages
2068-2076
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
To investigate the molecular basis that makes heterodimeric CD8alphabeta a more efficient coreceptor than homodimeric CD8alphaalpha, 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 CD8beta and that this allows partitioning of CD8alphabeta, but not of CD8alphaalpha, 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 CD8beta 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 CD3zeta in rafts and hence induces TCR signaling and T cell activation. This study shows that palmitoylation of CD8beta 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.
Keywords
4-Aminobenzoic Acid/immunology, Amino Acid Sequence, Animals, Antigens, CD3/metabolism, Antigens, CD8/immunology, Antigens, CD8/metabolism, Detergents, Enzyme Activation/immunology, H-2 Antigens/physiology, Hybridomas, Lymphocyte Activation, Lymphocyte Specific Protein Tyrosine Kinase p56(lck)/immunology, Lymphocyte Specific Protein Tyrosine Kinase p56(lck)/metabolism, Mice, Molecular Sequence Data, Palmitic Acid/metabolism, Peptide Fragments/immunology, Phosphorylation, Plasmodium berghei/immunology, Protein Structure, Tertiary, Protozoan Proteins/immunology, Receptors, Antigen, T-Cell/metabolism, Receptors, Antigen, T-Cell/physiology, T-Lymphocytes/immunology, T-Lymphocytes/metabolism
Pubmed
Web of science
Create date
28/01/2008 11:20
Last modification date
20/08/2019 12:35
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