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Cell-mediated Immune Responses01:40

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T Cell Activation and Clonal Selection01:22

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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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Updated: Jun 29, 2026

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

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Published on: October 22, 2012

Tuning T cell activation threshold and effector function with cross-reactive peptide ligands.

L B Nicholson1, A C Anderson, V K Kuchroo

  • 1Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA.

International Immunology
|February 2, 2000
PubMed
Summary

T cells exposed to a suboptimal peptide analog show hyperstimulation, leading to altered responses. Some T cells adapt to this hyperstimulation, increasing specificity and potentially impacting autoimmune disease regulation.

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Use of Single Chain MHC Technology to Investigate Co-agonism in Human CD8+ T Cell Activation

Published on: February 28, 2019

Area of Science:

  • Immunology
  • Autoimmunity
  • T cell biology

Background:

  • Myelin proteolipid protein (PLP) peptides are implicated in autoimmune diseases like multiple sclerosis.
  • T cell responses to autoantigens are crucial in the pathogenesis of autoimmune conditions.
  • Understanding T cell activation thresholds and ligand interactions is key to modulating immune responses.

Purpose of the Study:

  • To investigate how T cells adapt to stimulation by cross-reactive peptide ligands.
  • To explore the mechanisms underlying T cell hyperstimulation and desensitization.
  • To determine the implications of these findings for autoimmune disease development and regulation.

Main Methods:

  • Generation of cross-reactive T cells by immunizing mice with a modified PLP peptide (Q144).
  • In vitro expansion of T cells using a suboptimal, cross-reactive ligand (W144).
  • Analysis of T cell proliferation, cytokine secretion, and receptor expression upon stimulation with different peptides.

Main Results:

  • T cell clones expanded with W144 were hyperstimulated by the immunizing Q144 peptide, exhibiting a heteroclitic response.
  • Exposure to the hyperstimulating Q144 ligand induced desensitization in some T cells, increasing their activation threshold and specificity.
  • Long-term culture with Q144 led to CD4 receptor downregulation in some T cell clones.

Conclusions:

  • Exposure to suboptimal cross-reactive ligands modifies T cell activation thresholds and effector functions.
  • T cell desensitization can lead to a more specific T cell response, altering the immune repertoire.
  • These findings offer insights into T cell heteroclitic responses and have implications for managing autoimmune diseases.