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Related Concept Videos

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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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.
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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.
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Antigens Involved in Adaptive Immunity01:26

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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.
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B Cell Activation and Differentiation01:24

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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.
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Related Experiment Video

Updated: Aug 19, 2025

Measuring TCR-pMHC Binding In Situ using a FRET-based Microscopy Assay
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Discrete LAT condensates encode antigen information from single pMHC:TCR binding events.

Darren B McAffee1, Mark K O'Dair1, Jenny J Lin1

  • 1Department of Chemistry, University of California, Berkeley, Berkeley, CA, 94720, USA.

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T cell antigen discrimination relies on LAT protein condensation. A single binding event triggers a self-limiting condensate, with its formation probability, not size or lifetime, linked to binding duration, revealing insights into T cell specificity.

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Area of Science:

  • Immunology
  • Cell Biology
  • Biophysics

Background:

  • T cell recognition of antigens is crucial for adaptive immunity.
  • The linker for activation of T cells (LAT) protein forms 2D condensates, a key feature in T cell antigen discrimination.
  • Understanding the dynamics of LAT condensation and its relationship with T cell receptor (TCR) binding is essential.

Purpose of the Study:

  • To investigate the spatial and temporal dynamics of LAT condensation in response to pMHC:TCR binding events.
  • To determine how the duration of pMHC:TCR binding influences LAT condensate formation, size, and lifetime.
  • To elucidate the role of LAT condensation in setting antigen discrimination thresholds in T cells.

Main Methods:

  • Utilized single-molecule imaging techniques to track individual pMHC:TCR binding events.
  • Simultaneously monitored LAT condensation dynamics at the cell membrane.
  • Analyzed the correlation between pMHC:TCR binding dwell time and LAT condensate properties.

Main Results:

  • Individual pMHC:TCR binding events are sufficient to initiate LAT condensation.
  • LAT condensates are self-limiting, with size and lifetime independent of binding event duration.
  • The probability of LAT condensate formation correlates with pMHC:TCR binding dwell time.
  • LAT condensation occurs abruptly after a significant delay, and a mutation affecting PLC-γ1 recruitment alters this delay and T cell specificity.

Conclusions:

  • LAT protein condensation functions as a critical phase transition in T cell antigen discrimination.
  • The probability of LAT condensate formation, rather than its physical characteristics, is modulated by antigen binding dwell time.
  • LAT condensation dynamics play a role in establishing the thresholds for T cell antigen specificity.