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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...
B Cell Activation and Differentiation01:24

B Cell Activation and Differentiation

The adaptive immune response, a sophisticated defense mechanism, relies on the activation and differentiation of B lymphocytes, or B cells. These processes enable our bodies to mount a tailored response against specific pathogens such as bacteria, free virus particles, toxins, and parasites.
When naive B cells encounter a specific antigen that can bind to the B cell receptor (BCR) on their surface, they undergo sensitization to respond to the antigen's presence. Sensitization begins with...
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...
Receptor Tyrosine Kinases01:26

Receptor Tyrosine Kinases

Receptor tyrosine kinases or RTKs are membrane-bound receptors that phosphorylate specific tyrosine on protein substrates. RTKs regulate cellular growth, differentiation, survival, and migration. They contain an extracellular ligand binding domain, a transmembrane domain, and a cytosolic tail with intrinsic kinase activity. Several extracellular signaling molecules activate RTKs in one or more ways and relay the signal downstream. Ligands such as platelet-derived growth factor (PDGF) or...
Antigen Processing Pathways01:31

Antigen Processing Pathways

MHC molecules are key players in the immune response, enabling T cells to recognize and respond to specific antigens. They are present on the surface of all nucleated cells in the body and are instrumental in presenting antigens to T cells and activating them. T cells recognize the MHC-antigen complex and initiate an immune response. MHC class I and MHC class II are two main types of MHC molecules, each associated with a distinct antigen processing pathway.
MHC Class I: Presenting Endogenous...

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Related Experiment Video

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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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Mechanisms for T cell receptor triggering.

P Anton van der Merwe1, Omer Dushek

  • 1Sir William Dunn School of Pathology, University of Oxford, Oxford, UK. anton.vandermerwe@path.ox.ac.uk

Nature Reviews. Immunology
|December 4, 2010
PubMed
Summary
This summary is machine-generated.

T cell receptor (TCR) triggering mechanisms remain debated. Recent evidence suggests that aggregation, conformational change, and segregation may all contribute to TCR signal transduction, reflecting the need to detect rare foreign antigens amidst self-peptides.

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Area of Science:

  • Immunology
  • Molecular Biology
  • Cell Signaling

Background:

  • The T cell receptor (TCR) initiates adaptive immune responses upon recognizing foreign antigens.
  • The precise mechanism of TCR triggering, or signal transduction across the plasma membrane, is a subject of ongoing scientific debate.
  • Proposed mechanisms include ligand-induced receptor aggregation, conformational changes within the TCR complex, and segregation of signaling molecules within the cell membrane.

Purpose of the Study:

  • To review recent evidence supporting different proposed mechanisms of T cell receptor (TCR) triggering.
  • To synthesize current understanding of how TCRs transduce signals after binding to peptide-MHC ligands.
  • To explore the complexity of TCR-mediated antigen recognition in the context of signal detection and noise.

Main Methods:

  • Literature review of recently published studies on TCR triggering mechanisms.
  • Analysis of experimental evidence supporting aggregation, conformational change, and segregation models.
  • Synthesis of findings to evaluate the contribution of each proposed mechanism.

Main Results:

  • Evidence supports a role for receptor aggregation in TCR triggering.
  • Data also indicate that conformational changes within the TCR complex are involved in signal transduction.
  • Segregation of signaling molecules within lipid rafts or other membrane domains appears to be a relevant mechanism.

Conclusions:

  • All three proposed mechanisms—aggregation, conformational change, and segregation—likely contribute to T cell receptor (TCR) triggering.
  • The complex nature of TCR signaling is necessary to reliably detect weak foreign antigen signals amidst abundant self-peptides.
  • Understanding these mechanisms is crucial for deciphering immune responses and developing immunotherapies.