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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...
Primary Lymphoid Organs01:16

Primary Lymphoid Organs

Primary lymphoid organs are pivotal in the formation, development, and maturation of lymphocytes, the white blood cells that serve as the backbone of our immune system. This crucial function underscores their fundamental role in maintaining our overall health and immunity. The two primary lymphoid organs of prime importance are the red bone marrow and the thymus.
The red bone marrow is a soft, spongy tissue nestled in the interior of long bones such as the humerus and femur. It is the site...
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...
Role Of Notch Signalling In Intestinal Stem Cell Renewal01:12

Role Of Notch Signalling In Intestinal Stem Cell Renewal

Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...

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Related Experiment Video

Updated: Jun 5, 2026

Examination of Thymic Positive and Negative Selection by Flow Cytometry
14:29

Examination of Thymic Positive and Negative Selection by Flow Cytometry

Published on: October 8, 2012

Signaling in thymic selection.

Nicholas R J Gascoigne1, Ed Palmer

  • 1Department of Immunology and Microbial Science, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA. gascoigne@scripps.edu

Current Opinion in Immunology
|January 19, 2011
PubMed
Summary
This summary is machine-generated.

T cell receptor signaling in thymocytes determines T cell repertoire formation. Signal strength, duration, and protein Themis influence selection and lineage commitment, crucial for adaptive immunity.

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Area of Science:

  • Immunology
  • Cell Biology
  • Developmental Biology

Background:

  • T cell receptor (TCR) signaling is critical for thymocyte selection, shaping the mature T cell repertoire.
  • Lck kinase is essential for initiating TCR signaling, and much of it exists in an active state pre-signaling.
  • The strength of TCR-antigen binding may be translated into a digital signal via co-receptor interactions with Lck.

Purpose of the Study:

  • To elucidate the mechanisms by which TCR signal strength dictates thymocyte fate.
  • To investigate the role of Themis protein in positive selection.
  • To understand how signaling pathways and cytokine responsiveness influence CD4/CD8 lineage commitment.

Main Methods:

  • Analysis of TCR signaling dynamics and Lck kinase activity.
  • Investigating the downstream effects of signal strength on MAP kinase localization.
  • Studying the function of Themis in thymocyte development.
  • Examining the impact of ZAP-70 signaling and IL-7 on lineage commitment.

Main Results:

  • Signal strength and duration, mediated by TCR-co-receptor-Lck interactions, act as a digital switch for thymocyte selection.
  • MAP kinase signaling localization downstream of TCR engagement predicts positive or negative selection outcomes.
  • Themis protein plays a key role in facilitating passage through the positive selection checkpoint.
  • ZAP-70 signaling levels and IL-7 responsiveness are critical determinants of CD4 versus CD8 lineage commitment.

Conclusions:

  • TCR signaling strength and duration are digitally translated to control thymocyte selection.
  • Themis and regulated signaling pathways are essential for generating a functional T cell repertoire and appropriate lineage commitment.