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CD8 modulation of T-cell antigen receptor-ligand interactions on living cytotoxic T lymphocytes

I F Luescher1, E Vivier, A Layer

  • 1Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, Epalinges, Switzerland.

Nature
|January 26, 1995
PubMed

Insights

The CD8 molecule significantly enhances T-cell receptor (TCR) ligand binding avidity by coordinating interactions with major histocompatibility complex (MHC) class I molecules. This CD8-TCR interaction modulates T-cell activation dynamics and temperature dependence.

Area of Science:

  • Immunology
  • Molecular Biology
  • Cell Biology

Background:

  • Cytotoxic T lymphocytes (CTLs) primarily express alpha/beta CD8 heterodimers.
  • CD8 interacts with non-polymorphic regions of MHC class I molecules, mediating adhesion or acting as a coreceptor for TCR-ligand binding.
  • The precise mechanism by which CD8 enhances TCR-ligand interactions remains incompletely understood.

Purpose of the Study:

  • To investigate the role of CD8 in strengthening the avidity of T-cell receptor (TCR)-ligand interactions.
  • To elucidate the molecular basis for CD8's coreceptor function in T-cell activation.
  • To analyze the kinetic and dynamic impact of CD8 on TCR-ligand binding.

Main Methods:

  • TCR photoaffinity labeling using a photoreactive H-2Kd-peptide derivative complex.
  • Site-directed mutagenesis of the H-2Kd molecule (substitution of Asp 227 with Lys).
  • Kinetic analysis of TCR-ligand interactions on CD8+ and CD8- cytotoxic T cells.

Main Results:

  • CD8 significantly strengthens the avidity of TCR-ligand interactions on cloned cytotoxic T cells.
  • Coordinate binding of ligand molecules by both CD8 and TCR explains the enhanced avidity.
  • Substitution of Asp 227 in H-2Kd impaired TCR-ligand binding on CD8+ cells, highlighting its importance.
  • CD8 influences the dynamics and temperature dependence of TCR-ligand interactions.

Conclusions:

  • CD8 acts as a crucial coreceptor, enhancing TCR-ligand binding avidity through coordinate interactions.
  • CD8-TCR interactions modulate the kinetics and thermodynamics of T-cell activation.
  • The coreceptor function of CD8 can be modulated by its specific interactions with the TCR and MHC class I molecules.

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