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Related Concept Videos

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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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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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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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Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
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The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
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The cadherins are a superfamily of cell adhesion molecules comprising over 180 variants, with specific tissues expressing a particular combination of cadherin types. Cadherins generally exhibit homophilic binding; i.e., cadherins on one cell bind to cadherins of the same or closely related type on another cell. Thus, cells of the same type have a specific affinity to bind to each other and sort themselves into clusters to form tissues.
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Adenoviral Transduction of Naive CD4 T Cells to Study Treg Differentiation
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Nck adaptor proteins modulate differentiation and effector function of T cells.

Kun-Hui Lu1, Selina Keppler1, Frank Leithäuser1

  • 1*Molecular Immunology, German Cancer Research Center, Heidelberg, Germany; Lymphocyte Interaction Laboratory, London Research Institute-Cancer Research UK, London, United Kingdom; Department of Pathology, Universitätsklinikum, Ulm, Germany; Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada; Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.

Journal of Leukocyte Biology
|May 22, 2015
PubMed
Summary

Nck proteins are crucial for T cell function, impacting immune responses. Their absence impairs T follicular helper (Tfh) cell differentiation and antibody production, highlighting their role in adaptive immunity.

Keywords:
Tfhantibody productioncell deathfollicular helper Tgerminal center

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Area of Science:

  • Immunology
  • Molecular Biology
  • Cell Biology

Background:

  • T cell reactivity is key for immune responses and treating immune disorders.
  • Nck proteins act as cytoplasmic adaptors, influencing T cell receptor (TCR) signaling and T cell repertoire.
  • Nck proteins enhance TCR signal strength, affecting thymic selection and peripheral T cell sensitivity.

Purpose of the Study:

  • To investigate the role of Nck proteins in CD4(+) T cell differentiation and effector functions.
  • To analyze the impact of Nck deficiency on T follicular helper (Tfh) cell development and function.

Main Methods:

  • Utilized Nck.T(-/-) mice to study T cell differentiation and effector functions.
  • Immunized mice with T cell-dependent antigens to assess immune responses.
  • Analyzed T cell populations, cytokine production (IL-4, IL-10, IL-21), Akt phosphorylation, and antibody production.

Main Results:

  • Nck.T(-/-) mice showed impaired germinal center (GC) formation and reduced Tfh cells post-immunization.
  • Decreased levels of Th2/Tfh cytokines (IL-4, IL-10, IL-21) were observed in Nck.T(-/-) T cells.
  • Tfh cells in Nck.T(-/-) mice exhibited increased cell death, linked to reduced Akt phosphorylation, leading to impaired antibody production and affinity maturation.

Conclusions:

  • Nck proteins are essential for Tfh cell differentiation and effector functions.
  • Nck proteins play a significant role in adaptive immune responses, including antibody production.
  • Nck proteins contribute to both thymic selection and the regulation of peripheral CD4(+) T cell functions.