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A role for CD8 in the developmental tuning of antigen recognition and CD3 conformational change

Diana Gil1, Adam G Schrum, Mark A Daniels

  • 1Department of Immunology, College of Medicine, Mayo Clinic, Rochester, MN 55905, USA.

Journal of Immunology (Baltimore, Md. : 1950)
|March 7, 2008
PubMed

Insights

The CD8 coreceptor is essential for T cell receptor (TCR) signaling by enabling CD3 conformational changes (CD3Deltac) in T lineage cells. T cell maturation, marked by increased sialylation, reduces CD8 activity and T cell sensitivity.

Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • T cell receptor (TCR) engagement with peptide-MHC class I (pMHC) ligands triggers T cell signaling via conformational changes in CD3 (CD3Deltac).
  • The precise role of coreceptors in initiating this signaling cascade remains an area of active investigation.

Purpose of the Study:

  • To investigate the requirement of the CD8 coreceptor in generating CD3Deltac upon TCR/pMHC interaction.
  • To explore the impact of T cell maturation and sialylation on CD8-mediated CD3Deltac induction and T cell sensitivity.

Main Methods:

  • Studied T cell signaling in primary T lineage cells and antigen-presenting cells (APCs) using TCR/pMHC interactions.
  • Assessed the role of the CD8 coreceptor in CD3Deltac generation.
  • Analyzed the effects of antigen binding strength and Src kinase signaling.
  • Investigated the influence of T cell maturation-associated sialylation on CD8 activity and CD3Deltac induction.

Main Results:

  • CD8 coreceptor is required for CD3Deltac generation during TCR engagement with pMHC on primary T lineage cells and APCs.
  • CD8's activity in CD3Deltac induction is independent of enhanced antigen binding strength or Src kinase signaling.
  • Increased sialylation during T cell maturation attenuates Ag-induced CD3Deltac by limiting CD8 activity.
  • Both weak and strong ligands induced CD3Deltac in pre-TCR thymocytes, but only strong ligands were effective in mature T cells.

Conclusions:

  • CD8 physically regulates CD3Deltac induction by translating productive antigen encounters from the TCR to the CD3 complex.
  • Developmentally regulated CD8 sialylation tunes T cell sensitivity, influencing the threshold for T cell activation.

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