Decreased binding of peptides-MHC class I (pMHC) multimeric complexes to CD8 affects their binding avidity for the TCR but does not significantly impact on pMHC/TCR dissociation rate.

Details

Serval ID
serval:BIB_68A7C97BE100
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Decreased binding of peptides-MHC class I (pMHC) multimeric complexes to CD8 affects their binding avidity for the TCR but does not significantly impact on pMHC/TCR dissociation rate.
Journal
Journal of immunology
Author(s)
Dutoit V., Guillaume P., Ayyoub M., Hesdorffer C.S., Luescher I.F., Valmori D.
ISSN
0022-1767
Publication state
Published
Issued date
2003
Peer-reviewed
Oui
Volume
170
Number
10
Pages
5110-5117
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't - Publication Status: ppublish
Abstract
The CD8 coreceptor plays a crucial role in both T cell development in the thymus and in the activation of mature T cells in response to Ag-specific stimulation. In this study we used soluble peptides-MHC class I (pMHC) multimeric complexes bearing mutations in the CD8 binding site that impair their binding to the MHC, together with altered peptide ligands, to assess the impact of CD8 on pMHC binding to the TCR. Our data support a model in which CD8 promotes the binding of TCR to pMHC. However, once the pMHC/TCR complex is formed, the TCR dominates the pMHC/TCR dissociation rates. As a consequence of these molecular interactions, under physiologic conditions CD8 plays a key role in complex formation, resulting in the enhancement of CD8 T cell functions whose specificity, however, is determined by the TCR.
Keywords
Amino Acid Substitution, Antigens, CD8, Antigens, Neoplasm, CD8-Positive T-Lymphocytes, Clone Cells, Cytotoxicity, Immunologic, Down-Regulation, HLA-A2 Antigen, Humans, Kinetics, Lymphocyte Activation, Macromolecular Substances, Mutagenesis, Site-Directed, Neoplasm Proteins, Peptide Fragments, Protein Binding, Protein Structure, Tertiary, Receptors, Antigen, T-Cell, Tumor Cells, Cultured
Pubmed
Web of science
Create date
28/01/2008 11:19
Last modification date
20/08/2019 14:23
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