CD5 inhibits signaling at the immunological synapse without impairing its formation

Cédric Brossard1, Monique Semichon, Alain Trautmann

  • 1Département de Biologie Cellulaire, Institut National de la Santé et de la Recherche Médicale, Unité 567, Center National de la Recherche Scientifique, Unité Mixte de Recherche 8104, Université René Descartes, Institut Cochin, Paris, France.

Insights

CD5, a T cell inhibitory molecule, is recruited to the immunological synapse (IS). It reduces T cell responses to antigen presentation by affecting signaling, not synapse formation.

Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • T cell activation relies on antigen detection at the immunological synapse (IS).
  • CD5 is recognized as an inhibitory molecule in T cell signaling.
  • The role of CD5 within the IS during T cell activation remained unclear.

Purpose of the Study:

  • To investigate the recruitment and function of CD5 at the IS.
  • To determine CD5's impact on synapse formation and T cell signaling.

Main Methods:

  • Utilized video-imaging microscopy of fluorescently tagged CD5 and CD3 in T cells.
  • Analyzed CD5 recruitment kinetics (Ag-dependent and independent).
  • Assessed T cell adhesion, tyrosine phosphorylation, and calcium responses upon antigen recognition.

Main Results:

  • CD5 is rapidly recruited to the IS, colocalizing with CD3.
  • CD5 recruitment is partly antigen-independent and partly antigen-dependent.
  • CD5 expression did not alter CD3 recruitment, T cell-APC adhesion, or IS formation.
  • CD5 significantly decreased tyrosine phosphorylation and calcium signaling amplitude.
  • Inhibition correlated with CD5 membrane levels and required its ITAM motif.

Conclusions:

  • CD5 is dynamically recruited to the IS.
  • CD5 negatively regulates T cell activation by modulating downstream signaling pathways.
  • CD5 impacts T cell responsiveness without affecting the initial IS formation or adhesion.

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