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T Cell Activation and Clonal Selection01:22

T Cell Activation and Clonal Selection

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.
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Peptide:MHC Tetramer-based Enrichment of Epitope-specific T cells
13:58

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Published on: October 22, 2012

Epitope density influences CD8+ memory T cell differentiation.

Julie Leignadier1, Nathalie Labrecque

  • 1Maisonneuve-Rosemont Hospital Research Center, University of Montreal, Montreal, Quebec, Canada.

Plos One
|November 10, 2010
PubMed
Summary
This summary is machine-generated.

Antigen dose impacts memory CD8(+) T cell numbers, not effector function. Lower antigen exposure fine-tunes T cell receptor signaling, influencing transcription factors like Eomes and Bcl6 for enhanced memory cell persistence.

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Area of Science:

  • Immunology
  • Cellular Biology
  • Vaccinology

Background:

  • Long-lived memory T cells are crucial for effective vaccination.
  • Factors influencing CD8(+) T cell differentiation into memory cells are not fully understood.
  • This study investigates the role of T cell receptor (TCR) signaling strength in memory CD8(+) T cell generation.

Purpose of the Study:

  • To determine if TCR signaling strength, modulated by antigen dose, affects memory CD8(+) T cell generation.
  • To elucidate the molecular mechanisms underlying antigen dose-dependent memory T cell differentiation.
  • To understand how antigen presentation by dendritic cells influences T cell fate.

Main Methods:

  • Manipulating antigenic epitope density presented by dendritic cells to mouse naïve CD8(+) T cells.
  • Maintaining constant TCR affinity while varying antigen dose.
  • Analyzing T cell expansion, effector function acquisition, and transcription factor expression (Eomes, Bcl6, Nor-1).

Main Results:

  • A two-fold decrease in antigen dose selectively reduced memory CD8(+) T cell generation without affecting T cell expansion or effector functions.
  • Low antigen dose altered T cell-dendritic cell interaction duration and modulated Eomes and Bcl6 expression.
  • Higher epitope density priming led to decreased Nor-1 expression, reduced Bcl-2 conversion to pro-apoptotic forms, and increased memory T cell numbers.

Conclusions:

  • Antigen dose encountered by naïve CD8(+) T cells influences the number of persistent memory CD8(+) T cells, not the generation of functional effector cells.
  • Antigenic epitope density sensed during priming modulates Bcl6, Eomes, and Nor-1 expression.
  • This modulation provides a mechanism by which antigen dose regulates memory T cell generation and persistence.