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Related Concept Videos

T Cell Activation and Clonal Selection01:22

T Cell Activation and Clonal Selection

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...
T Cell Types and Functions01:24

T Cell Types and Functions

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.
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
B Cell Activation and Differentiation01:24

B Cell Activation and Differentiation

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.
When naive B cells encounter a specific antigen that can bind to the B cell receptor (BCR) on their surface, they undergo sensitization to respond to the antigen's presence. Sensitization begins with...
Anaphase Promoting Complex00:50

Anaphase Promoting Complex

The stepwise destruction of specific proteins is necessary for the progression and completion of the cell cycle. Such proteins are ubiquitinated by ubiquitin ligases and then subsequently destroyed by the proteasome. The SCF (Skp1/Cullin/F-box) and the anaphase-promoting complex (APC) are two important ubiquitin ligases involved in cell cycle progression. While SCF is active throughout the cell cycle, APC gets activated during metaphase to anaphase transition. Cdc20 or Cdh1 binds to APC and...
Cytotoxic T Cells-mediated Immune Response01:27

Cytotoxic T Cells-mediated Immune Response

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.
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...

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Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries
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CD5-dependent CK2 activation pathway regulates threshold for T cell anergy.

Christine M Sestero1, Donald J McGuire, Patrizia De Sarno

  • 1Division of Clinical Immunology and Rheumatology, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA.

Journal of Immunology (Baltimore, Md. : 1950)
|August 21, 2012
PubMed
Summary

CD5-CK2 signaling regulates T cell responsiveness and the generation of Th2 and Th17 cells. This pathway is crucial for setting T cell activation thresholds and immune responses, impacting conditions like experimental autoimmune encephalomyelitis.

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Area of Science:

  • Immunology
  • Molecular Biology
  • Cell Signaling

Background:

  • CD5 is a transmembrane glycoprotein that plays a critical role in T cell development and signaling.
  • CD5 interacts with casein kinase 2 (CK2), a serine/threonine kinase, influencing T cell activation thresholds.
  • Understanding the CD5-CK2 interaction's physiological significance is vital for T cell immunology.

Purpose of the Study:

  • To investigate the physiological role of CD5-dependent CK2 activation in T cells.
  • To determine how the CD5-CK2 interaction impacts T cell development, activation, and differentiation.
  • To assess the role of CD5-CK2 signaling in autoimmune disease models.

Main Methods:

  • Generation of a knock-in mouse model (CD5ΔCK2BD) with a selective inability to interact with CK2.
  • Analysis of T cell populations in thymus and peripheral lymphoid organs of CD5ΔCK2BD and wild-type (WT) mice.
  • In vitro T cell stimulation assays and in vivo experimental autoimmune encephalomyelitis (EAE) model.

Main Results:

  • CD5ΔCK2BD mice showed reduced double-positive thymocytes but normal peripheral T cell populations.
  • CD5ΔCK2BD T cells exhibited hypoproliferation and enhanced activation-induced cell death upon stimulation.
  • CD5-CK2 signaling was essential for naive CD4+ T cell differentiation into Th2 and Th17 cells, but not Th1 cells.
  • CD5ΔCK2BD mice recapitulated the reduced EAE severity and delayed onset observed in CD5 knockout mice.
  • CD5WT mice demonstrated tolerance induction with increased peptide dose, a phenomenon absent in CD5ΔCK2BD mice.

Conclusions:

  • CD5-CK2 signaling is a critical determinant of T cell responsiveness, setting the threshold for activation.
  • This pathway is indispensable for the efficient generation of Th2 and Th17 effector cells.
  • CD5-CK2 signaling plays a significant role in regulating autoimmune disease pathogenesis.