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Interaction between the CD8 coreceptor and major histocompatibility complex class I stabilizes T cell
Linda Wooldridge1, Hugo A van den Berg, Meir Glick
1T Cell Modulation Group, Nuffield Department of Medicine, Peter Medawar Building for Pathogen Research, University of Oxford, South Parks Road, Oxford OX1 3SY, United Kingdom.
The Journal of Biological Chemistry
|April 20, 2005
Summary
The CD8 coreceptor stabilizes T cell receptor (TCR) interactions with peptide-major histocompatibility complex class I (pMHCI) ligands. This stabilization is crucial for TCR triggering, particularly with low-affinity ligands, impacting T cell cross-reactivity.
Area of Science:
- Immunology
- Molecular Biology
- Biophysics
Background:
- The T cell receptor (TCR) interaction with peptide-major histocompatibility complex class I (pMHCI) is critical for T cell activation.
- The off-rate (k(off)) and half-life of this interaction are key determinants of biological outcomes.
- The role of the CD8 coreceptor in modulating TCR/pMHCI dissociation kinetics remains unclear.
Purpose of the Study:
- To investigate whether the CD8 coreceptor influences the dissociation kinetics of the TCR/pMHCI interaction.
- To quantify the contribution of CD8 to TCR/pMHCI dissociation in membrane-constrained settings.
Main Methods:
- Utilized engineered pMHCI mutants with a >1,000-fold range of CD8 affinities.
- Quantified CD8's contribution to TCR/pMHCI dissociation.
- Employed data modeling to derive a "stabilization factor".
Main Results:
- CD8 binding significantly influences TCR/pMHCI dissociation.
- A "stabilization factor" was identified, preferentially enhancing TCR triggering for low-affinity pMHCI ligands.
- CD8's contribution is most pronounced in membrane-constrained interactions.
Conclusions:
- CD8 plays a critical role in stabilizing TCR/pMHCI interactions.
- CD8's influence on TCR triggering kinetics is ligand-dependent.
- This CD8-mediated stabilization may be a key mechanism underlying T cell cross-reactivity.