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Related Concept Videos

T Cell Activation and Clonal Selection01:22

T Cell Activation and Clonal Selection

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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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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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The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
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Integrins bind ligands and transmit information from outside the cell to inside or vice-versa through an "outside-in signaling" or "inside-out signaling."
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Updated: Jun 13, 2025

Real-time Live Imaging of T-cell Signaling Complex Formation
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LAT encodes T cell activation pathway balance.

Adam J Rubin1,2,3, Tyler T Dao1,2,3,4, Amelia V Schueppert1,2,3

  • 1Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.

Biorxiv : the Preprint Server for Biology
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Investigating the linker for activation of T cells (LAT) protein, scientists mapped its sequence-function relationship. They discovered widely distributed functional regions and a precise molecular organization that constrains T cell signaling outputs.

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Area of Science:

  • Immunology
  • Molecular Biology
  • Systems Biology

Background:

  • Immune cells, particularly T cells, rely on complex signaling cascades initiated by T cell receptors (TCRs) to detect specific peptide antigens presented by Human Leukocyte Antigen (HLA).
  • The linker for activation of T cells (LAT) protein acts as a crucial TCR-proximal adapter, organizing signaling partners and propagating signals through pathways like NFAT and AP-1.

Purpose of the Study:

  • To comprehensively profile the sequence-function relationship of the LAT protein and understand how its amino acid sequence encodes balanced downstream pathway activation.
  • To investigate the molecular basis for balanced signaling defects observed in LAT mutants.

Main Methods:

  • Development of a pooled, single-cell, high-content screening approach to analyze a large series of LAT mutants.
  • Measurement of epigenetic, transcriptomic, and cell surface protein dynamics in single cells harboring distinct LAT mutants.
  • Utilized proximal protein labeling to investigate LAT protein interactions.

Main Results:

  • Identified functional regions spanning over 40% of the LAT amino acid sequence, with conserved motifs and charge distribution being critical features.
  • Observed that most LAT mutants, regardless of position, confer balanced defects across downstream signaling pathways (NFAT, AP-1).
  • Demonstrated that disruption of a single LAT interaction can indirectly affect other interactions, highlighting the protein's role in organizing signaling complexes.

Conclusions:

  • The LAT protein possesses widely distributed functional regions within its disordered structure, and its precise physical organization with interacting molecules constrains signaling outputs.
  • The study presents a novel approach for interrogating sequence-function relationships in proteins with complex activities across multiple regulatory layers.