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Related Concept Videos

T Cell Activation and Clonal Selection01:22

T Cell Activation and Clonal Selection

753
T cells are integral to our adaptive immune system, recognizing and effectively responding to foreign antigens. T cell activation and clonal selection are pivotal in orchestrating this immune response. This article elucidates these mechanisms, detailing the roles of cluster of differentiation (CD) markers, major histocompatibility complex (MHC) molecules, costimulatory signals, and the process of clonal selection.
Naive T cells that have not yet encountered an antigen express two primary CD...
753

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CD3 downregulation identifies high-avidity human CD8 T cells.

Genevieve T Clutton1, Ann Marie K Weideman2, Melissa A Mischell2

  • 1Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.

Clinical and Experimental Immunology
|November 11, 2023
PubMed
Summary

High-avidity CD8 T cells, crucial for fighting infections and cancer, can be identified by measuring CD3 downmodulation. This simple flow cytometry method correlates strongly with T-cell receptor (TCR) avidity.

Keywords:
CD8 + T cellsT-cell receptorsanti-viral immunityhumantumor immunology

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Area of Science:

  • Immunology
  • Cellular Biology
  • Molecular Medicine

Background:

  • CD8 T cells are critical for adaptive immunity, recognizing pathogen- or tumor-associated antigens presented by peptide-MHC complexes.
  • The T-cell receptor (TCR) affinity for peptide-MHC influences CD8 T cell sensitivity, termed functional avidity.
  • TCR-CD3 complex and CD8 co-receptor expression are downregulated upon T-cell activation.

Purpose of the Study:

  • To investigate the relationship between CD3 and CD8 downmodulation and the functional avidity of human CD8 T cells.
  • To determine if CD3 downmodulation can serve as a reliable marker for identifying high-avidity CD8 T cells.

Main Methods:

  • Human CD8 T cells were stimulated with viral peptides (CMV, EBV, HIV) across various MHC restrictions.
  • Quantification of CD3 and CD8 downmodulation using flow cytometry.
  • Analysis of TCR-transduced T cells engineered to target a tumor-associated antigen.

Main Results:

  • A strong correlation was observed between CD3/CD8 downmodulation levels and CD8 T cell functional avidity, irrespective of viral peptide origin.
  • Modifying TCR-peptide affinity in engineered T cells altered CD3 and CD8 downmodulation.
  • CD3 downmodulation emerged as a more robust correlate of T-cell avidity compared to CD8 downmodulation.

Conclusions:

  • CD3 downmodulation is a reliable indicator of CD8 T cell functional avidity.
  • Simple measurement of CD3 downmodulation via flow cytometry can identify high-avidity CD8 T cells for clinical applications.