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Related Concept Videos

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.
Naive T cells that have not yet encountered an antigen express two primary CD...
Diversity of Antigen Receptors01:28

Diversity of Antigen Receptors

Antigen receptors are essential components of the immune system crucial in defending the body against foreign invaders. These receptors are present on the surface of B and T cells, enabling them to recognize antigens and mount an appropriate immune response.
Before encountering any antigen, lymphocytes express these receptors. On B cells, the antigen receptor is a membrane-bound antibody molecule called BCR; on T cells, it is a T cell receptor or TCR. B and T cell receptors are composed of two...
T Cell Types and Functions01:24

T Cell Types and Functions

When T cells with CD4 markers are activated, they give rise to two types of effector cells: helper T cells and regulatory T cells. Meanwhile, T cells with CD8 markers differentiate into effector cytotoxic T cells. The differentiation of CD4 T cells into helper T cell subsets, such as Th1, Th2, and Th17 cells, is dependent on the antigen type, antigen-presenting cell, and regulatory cytokines.
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
Cytotoxic T Cells-mediated Immune Response01:27

Cytotoxic T Cells-mediated Immune Response

Cytotoxic T cells are a vital component of the immune system. They have the remarkable ability to identify and target antigens on infected or abnormal cells. These antigens often originate from intracellular pathogens such as viruses or abnormal proteins cancer cells produce.
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...
Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR activation may...
Antigens Involved in Adaptive Immunity01:26

Antigens Involved in Adaptive Immunity

An antigen is any substance the immune system identifies as foreign and potentially harmful to the body, prompting an immune response. Antigens have two functional properties: immunogenicity and reactivity. Immunogenicity is the ability of an antigen to stimulate a specific immune response. At the same time, reactivity describes the antigen's ability to react with the cells and antibodies produced in response to it.
Complete Antigens
Complete antigens possess both immunogenicity and reactivity.

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Using X-ray Crystallography, Biophysics, and Functional Assays to Determine the Mechanisms Governing T-cell Receptor Recognition of Cancer Antigens
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Coreceptor CD8-driven modulation of T cell antigen receptor specificity.

Hugo A van den Berg1, Linda Wooldridge, Bruno Laugel

  • 1Warwick Systems Biology Centre, Coventry House, University of Warwick, Coventry CV4 7AL, UK. hugo@maths.warwick.ac.uk

Journal of Theoretical Biology
|September 18, 2007
PubMed
Summary

CD8 coreceptor binding influences T cell receptor (TCR) sensitivity and affinity for peptide-major histocompatibility class I (pMHCI) ligands. This dynamic focusing mechanism enhances TCR repertoire diversity by allowing specific agonist avidity modulation.

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

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Using X-ray Crystallography, Biophysics, and Functional Assays to Determine the Mechanisms Governing T-cell Receptor Recognition of Cancer Antigens
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Use of Single Chain MHC Technology to Investigate Co-agonism in Human CD8+ T Cell Activation
12:09

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
  • Molecular Biology
  • Cell Biology

Background:

  • The CD8 coreceptor is crucial for T cell recognition of peptide-major histocompatibility class I (pMHCI) complexes.
  • Understanding CD8's role in modulating T cell receptor (TCR) interactions is key to deciphering immune responses.

Purpose of the Study:

  • To investigate how CD8 influences TCR/pMHCI binding affinity and TCR sensitivity.
  • To explore the mechanism by which CD8 regulates T cell functional avidity towards different agonists.

Main Methods:

  • Analysis of TCR/pMHCI binding kinetics (association and dissociation rates).
  • Mathematical modeling to assess CD8's impact on TCR triggering thresholds.
  • Investigating recruitment of TCR/pMHCI complexes to membrane microdomains.

Main Results:

  • CD8 modifies TCR/pMHCI binding affinity by altering association and dissociation rates.
  • CD8 modulates TCR sensitivity by recruiting complexes to membrane microdomains, dependent on CD8/pMHCI affinity.
  • T cells can dynamically adjust functional avidity for specific agonists via CD8 regulation.

Conclusions:

  • CD8-mediated ligand focusing allows dynamic tuning of TCR avidity, enabling recognition of diverse agonists while preventing autoimmunity.
  • This mechanism significantly expands the functional diversity of the T cell receptor repertoire.