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Developmental control of T-cell receptor internalization

F Luton1, M Buferne, A M Schmitt-Verhulst

  • 1Centre d'Immunologie INSERM-CNRS de Marseille-Luminy, France.

Thymus
|January 1, 1994
PubMed
Summary
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Ligand-induced T cell receptor (TCR)/CD3 internalization differs between mature and immature T cells. Protein tyrosine kinase (PTK) inhibition affects TCR/CD3 internalization in mature T cells but not in immature thymocytes.

Area of Science:

  • Immunology
  • Cell Biology

Background:

  • T cell receptor (TCR)/CD3 modulation is implicated in T cell tolerance induction.
  • Understanding TCR/CD3 internalization mechanisms is crucial for T cell function.

Purpose of the Study:

  • To compare ligand-induced TCR/CD3 internalization in a cytotoxic T lymphocyte (CTL) clone, immature thymocytes, and mature T cells.
  • To investigate the role of protein tyrosine kinases (PTKs) and protein kinase C (PKC) in this process.

Main Methods:

  • Utilized a monoclonal antibody (mAb) specific for the TCR (anti-Ti mAb) to trigger internalization.
  • Assessed internalization rates and inhibition by PTK inhibitor genistein and PKC inhibitor staurosporine.
  • Analyzed TCR/CD3 associated kinase activity and phosphorylation of CD3 components in immunoprecipitates.

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Main Results:

  • CD8+ splenocytes and CTL clones showed low-rate TCR/CD3 internalization, inhibited by genistein and staurosporine.
  • CD4+CD8+ thymocytes exhibited high-rate TCR/CD3 internalization, insensitive to genistein or staurosporine.
  • Genistein inhibited TCR/CD3 surface redistribution preceding internalization in the CTL clone.
  • Kinase activity in anti-Ti mAb immunoprecipitates phosphorylated CD3 components (gamma, delta, epsilon, zeta) in both cell types, with differential substrate phosphorylation.

Conclusions:

  • TCR/CD3 internalization mechanisms differ significantly between mature and immature T cells.
  • PTKs play a role in TCR/CD3 internalization and surface redistribution in mature T cells.
  • Specific PTKs like p56lck and p59fyn are associated with CD3 components in both T cell types.