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Related Concept Videos

Cells of the Innate Immune Response01:28

Cells of the Innate Immune Response

The innate immune response is an immediate and non-specific response against pathogens, acting swiftly to prevent the spread of infections. The primary cells involved in this response are phagocytes and natural killer (NK) cells.
Phagocytes
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An antigen is any substance the immune system identifies as foreign and potentially harmful to the body, prompting an immune response. Antigens have two functional properties: immunogenicity and reactivity. Immunogenicity is the ability of an antigen to stimulate a specific immune response. At the same time, reactivity describes the antigen's ability to react with the cells and antibodies produced in response to it.
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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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An Efficient and High Yield Method for Isolation of Mouse Dendritic Cell Subsets
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Cytokines regulate proteolysis in major histocompatibility complex class II-dependent antigen presentation by

E Fiebiger1, P Meraner, E Weber

  • 1Division of Immunology, Allergy, and Infectious Diseases, Department of Dermatology, University of Vienna Medical School, Austria.

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Pro-inflammatory cytokines boost endolysosomal protease activity in dendritic cells, enhancing antigen presentation. Anti-inflammatory cytokines suppress this activity, impairing antigen presentation and T cell receptor interactions.

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Area of Science:

  • Immunology
  • Cell Biology
  • Protease biochemistry

Background:

  • Endolysosomal proteases are crucial for antigen processing and presentation by major histocompatibility complex (MHC) class II molecules.
  • Dendritic cells (DCs) play a central role in initiating adaptive immune responses through antigen presentation.

Purpose of the Study:

  • To investigate the impact of pro-inflammatory and anti-inflammatory cytokines on endolysosomal protease activity in dendritic cells.
  • To determine how cytokine-mediated protease modulation affects MHC class II dimer formation, antigen degradation, and T cell receptor engagement.

Main Methods:

  • Treatment of human dendritic cells with tumor necrosis factor alpha, interleukin-1beta, and interleukin-10.
  • Assay of cathepsin S and cathepsin B activity.
  • Analysis of MHC class II sodium dodecyl sulfate-stable dimer formation.
  • Measurement of T cell receptor downregulation in antigen-specific T cell clones upon exposure to tetanus toxoid.

Main Results:

  • Pro-inflammatory cytokines (TNF-alpha, IL-1beta) rapidly increased cathepsin S and cathepsin B activity in DCs.
  • This protease activation led to increased MHC class II dimer formation in a cathepsin S-dependent manner.
  • Anti-inflammatory cytokine IL-10 suppressed cathepsin S and B activity, delaying MHC class II dimer formation and impairing antigen degradation.
  • IL-10 treatment reduced the availability of MHC class II-peptide complexes for T cell receptor recognition.

Conclusions:

  • Cytokine-mediated regulation of endolysosomal protease activity is a key mechanism controlling antigen presentation by dendritic cells.
  • Pro-inflammatory cytokines enhance antigen presentation by activating proteases, while anti-inflammatory cytokines dampen it.
  • This finding highlights a critical checkpoint in immune response modulation at the level of antigen processing.