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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.
Naive T cells that have not yet encountered an antigen express two primary CD...
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TGF - β Signaling Pathway01:16

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The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
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BTLA and PD-1 signals attenuate TCR-mediated transcriptomic changes.

Muhammad Zainul Arifin1, Judith Leitner2, Donagh Egan1

  • 1Systems Biology Ireland, School of Medicine, University College Dublin, Belfield, Dublin 4, Ireland.

Iscience
|July 18, 2024
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Immune checkpoints like PD-1 and BTLA dampen T cell receptor signaling. BTLA more strongly suppresses gene expression changes than PD-1, highlighting their role in cancer therapy.

Keywords:
Molecular biologyTranscriptomics

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Area of Science:

  • Immunology
  • Molecular Biology
  • Cancer Therapy

Background:

  • Immune checkpoints, including PD-1 and BTLA, are crucial targets in cancer immunotherapy.
  • T cell receptor (TCR) signaling orchestrates significant transcriptomic alterations.

Purpose of the Study:

  • To investigate the transcriptomic modifications induced by PD-1 and BTLA signaling in human T cells.
  • To compare the attenuating effects of PD-1 and BTLA on TCR-mediated gene expression.

Main Methods:

  • Utilized a human T cell reporter line to monitor gene expression changes.
  • Analyzed transcriptomic profiles following TCR-complex stimulation alone and in combination with PD-1 or BTLA signaling.

Main Results:

  • TCR stimulation led to both gene upregulation and repression.
  • PD-1 and BTLA signaling attenuated TCR-induced transcriptomic changes, suppressing upregulated genes and increasing expression of downregulated genes.
  • BTLA demonstrated a stronger attenuating effect than PD-1.
  • Significant overlap in regulated genes suggests quantitative differences between PD-1 and BTLA.

Conclusions:

  • PD-1 and BTLA act as negative regulators of TCR-mediated transcriptomic responses.
  • The findings underscore the role of these immune checkpoints in modulating T cell activation and provide insights for cancer therapy strategies.