CD8 enhances formation of stable T-cell receptor/MHC class I molecule complexes
Autor: | Ian A. Wilson, Anders Brunmark, Luc Teyton, Francis R. Carbone, Per A. Peterson, C.A. Scott, K C Garcia |
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Rok vydání: | 1996 |
Předmět: |
Stereochemistry
Protein Conformation T cell CD8 Antigens Receptors Antigen T-Cell alpha-beta chemical and pharmacologic phenomena Biology Major histocompatibility complex CD3 Complex Cell Line Mice Antigen MHC class I medicine Animals Histocompatibility Antigen H-2D Multidisciplinary Binding Sites T-cell receptor H-2 Antigens Histocompatibility Antigens Class II hemic and immune systems MHC restriction Cell biology medicine.anatomical_structure Drosophila melanogaster Models Chemical biology.protein Electrophoresis Polyacrylamide Gel Peptides Dimerization CD8 |
Zdroj: | Nature. 384(6609) |
ISSN: | 0028-0836 |
Popis: | T-cell antigen receptors (TCR) generally interact with moderate affinity with the complex formed by major histocompatibility complex (MHC) molecules and foreign peptides. MHC/TCR recognition is followed by the generation of a signal to the T cell through a monomorphic multicomponent system that includes the CD3 complex and accessory molecules such as CD4 and CD8. The interaction between the extracellular domains of MHC and TCR molecules, and the interaction of MHC and CD4/CD8 molecules, have been considered to occur independently of one another. We report here that the affinity of CD8 dimers for MHC class I molecules is independent of haplotype and peptide content, and that the affinity of the TCR for its specific ligand is enhanced through a reduced 'off' rate in the presence of either CD8alpha alpha homo- or CD8alpha beta heterodimers. Moreover, CD8 seems to help recognition of the specific MHC-peptide complex either by guiding an energetically favourable docking of TCR onto MHC, or by inducing conformational changes in the MHC complex that can augment the TCR/MHC-peptide interaction. CD8 should therefore be considered as an active participant in the T-cell recognition complex, rather than simply as an accessory molecule. |
Databáze: | OpenAIRE |
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