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Related Concept Videos

Tumor Immunotherapy01:27

Tumor Immunotherapy

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Immunotherapy is a treatment that boosts or manipulates the immune system to fight diseases, including cancer. For instance, by stimulating an immune response through vaccinations against viruses that cause cancers, like hepatitis B virus and human papillomavirus, these diseases can be prevented. Nonetheless, some cancer cells can avoid the immune system due to their rapid mutation and division. The immune response to many cancers involves three phases: elimination, equilibrium, and escape.
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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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The adaptive immune system, a crucial component of the overall immune response, offers a highly specialized defense against pathogens. It involves specific cell types and features, enabling it to combat infections effectively and efficiently.
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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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Autocrine Signaling01:01

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Autocrine signaling is one of the many signaling mechanisms that function inside multicellular organisms to carry out intercellular communication. In this type of signaling mechanism, the same cell that secretes an extracellular signaling molecule also expresses the receptors to bind and respond to that signaling molecule.
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Related Experiment Video

Updated: Mar 4, 2026

A Syngeneic Mouse B-Cell Lymphoma Model for Pre-Clinical Evaluation of CD19 CAR T Cells
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T Cell Receptor Signaling and Immune Tolerance: From Autoimmunity to Cancer Immunity.

Atsushi Tanaka1,2, Shimon Sakaguchi1,3

  • 1Laboratory of Experimental Immunology, Immunology Frontier Research Center, The University of Osaka, Suita, Japan;

Annual Review of Immunology
|March 2, 2026
PubMed
Summary
This summary is machine-generated.

T cell receptor (TCR) signaling intensity dictates T cell selection and activation, influencing immune deficiency and autoimmunity. Modulating TCR signaling offers therapeutic potential for autoimmune diseases and cancer immunity.

Keywords:
T cell receptor signalingTCR signalingTreg cellsZAP-70autoimmune diseasecancer immunityregulatory T cellsthymic T cell selection

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Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries
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Area of Science:

  • Immunology
  • Molecular Biology
  • Cell Biology

Background:

  • T cell receptor (TCR) signaling intensity is crucial for T cell development and function.
  • Dysregulated TCR signaling contributes to a spectrum of immune disorders, including autoimmunity.
  • Regulatory T cells (Treg) and conventional T cells (Tconv) are both impacted by TCR signal strength.

Purpose of the Study:

  • To investigate the consequences of graded TCR signal reduction on T cell selection and activation.
  • To explore the role of TCR signaling in the development of autoimmune diseases.
  • To evaluate the therapeutic potential of modulating TCR signaling in autoimmunity and cancer.

Main Methods:

  • Analysis of T cell selection and activation in response to varying TCR signal intensities.
  • Utilizing models of TCR signal attenuation, such as ZAP-70 hypomorphic mutations.
  • Investigating the effects of pharmacological TCR signal attenuation on peripheral T cells.

Main Results:

  • Reduced TCR signaling shifts the T cell repertoire towards self-reactivity and impairs Treg cell generation.
  • TCR signal attenuation can lead to spontaneous T cell-mediated autoimmune and inflammatory diseases.
  • Pharmacological TCR signal reduction can selectively deplete Treg cells and enhance anti-tumor immunity.

Conclusions:

  • TCR-proximal signaling is a critical regulator of T cell homeostasis and immune responses.
  • Targeting TCR signaling presents a promising strategy for managing autoimmune diseases.
  • Modulation of TCR signaling holds potential for improving cancer immunotherapy.