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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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T Cell Types and Functions01:24

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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.
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Cytotoxic T cells are a vital component of the immune system. They have the remarkable ability to identify and target antigens on infected or abnormal cells. These antigens often originate from intracellular pathogens such as viruses or abnormal proteins cancer cells produce.
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The JAK-STAT Signaling Pathway01:20

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Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
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MAPK Signaling Cascades01:07

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Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
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cAMP-dependent Protein Kinase Pathways01:25

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Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...
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Related Experiment Video

Updated: Aug 22, 2025

Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries
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Enhanced T cell effector activity by targeting the Mediator kinase module.

Katherine A Freitas1,2, Julia A Belk3, Elena Sotillo2

  • 1Immunology Graduate Program, Stanford University School of Medicine, Stanford, CA, USA.

Science (New York, N.Y.)
|November 10, 2022
PubMed
Summary

Researchers identified MED12 and CCNC as key genes limiting T cell function in cancer immunotherapy. Deleting MED12 boosts antitumor activity, offering a new target for enhancing T cell responses.

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Area of Science:

  • Immunology
  • Molecular Biology
  • Cancer Research

Background:

  • T cells are crucial for cancer regression.
  • Identifying factors limiting T cell function is vital for improving immunotherapies.

Purpose of the Study:

  • To identify genes that limit T cell function in engineered T cells.
  • To explore the role of the Mediator kinase module in T cell effector programming.

Main Methods:

  • Genome-wide CRISPR knockout screens were performed in human chimeric antigen receptor (CAR) T cells.
  • MED12 and CCNC were identified as top hits limiting T cell function.
  • Targeted MED12 deletion and CDK8/19 kinase inhibition were investigated.

Main Results:

  • Targeted MED12 deletion enhanced antitumor activity and sustained effector phenotype in engineered T cells.
  • Inhibition of CDK8/19 kinase activity increased non-engineered T cell expansion.
  • MED12-deficient T cells showed increased Mediator chromatin occupancy and IL2RA expression.

Conclusions:

  • The Mediator kinase module plays a significant role in T cell effector programming.
  • Targeting MED12 and related kinases presents a promising strategy for enhancing antitumor T cell potency.