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Related Concept Videos

Antigen Processing Pathways01:31

Antigen Processing Pathways

MHC molecules are key players in the immune response, enabling T cells to recognize and respond to specific antigens. They are present on the surface of all nucleated cells in the body and are instrumental in presenting antigens to T cells and activating them. T cells recognize the MHC-antigen complex and initiate an immune response. MHC class I and MHC class II are two main types of MHC molecules, each associated with a distinct antigen processing pathway.
MHC Class I: Presenting Endogenous...
Antigen Presenting Cells01:22

Antigen Presenting Cells

The immune system is a complex network of cells and molecules that protects the body from foreign invaders. T cells, a type of white blood cell, play a crucial role in this process. They recognize and attack foreign substances, such as pathogens, that enter the body.
T cells require the help of antigen-presenting cells (APCs), which process foreign antigens into smaller fragments that can be recognized by T cells. These APCs are highly specialized cells that efficiently internalize antigens...
Antigens Involved in Adaptive Immunity01:26

Antigens Involved in Adaptive Immunity

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.
Complete Antigens
Complete antigens possess both immunogenicity and reactivity.
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...
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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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Cathepsin S dominates autoantigen processing in human thymic dendritic cells.

Christina Stoeckle1, Paula Quecke, Thomas Rückrich

  • 1Hertie Institute for Clinical Brain Research, University of Tuebingen, Germany. christina.stoeckle@web.de

Journal of Autoimmunity
|March 20, 2012
PubMed
Summary

Thymic antigen presenting cells (APC) use lysosomal proteases to shape T cell selection. Cathepsin S in dendritic cells destroys self-epitopes, potentially allowing autoreactive T cells to escape negative selection and contribute to autoimmunity.

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Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • T cell development relies on thymocyte interactions with peptide-MHC complexes on thymic antigen presenting cells (APC).
  • Lysosomal proteases, like cathepsins, generate peptides for MHC II presentation but can also destroy T cell epitopes, impacting self-tolerance.
  • Dysfunctional epitope processing can lead to the escape of autoreactive T cells, potentially causing autoimmunity.

Purpose of the Study:

  • To investigate the antigen processing machinery and epitope generation/destruction in human thymic APC.
  • To understand how different APC subsets process autoantigens and influence T cell selection.
  • To identify key proteases involved in shaping the self-epitope repertoire presented during T cell development.

Main Methods:

  • Analysis of lysosomal protease expression in different thymic APC subsets.
  • Study of autoantigen processing by myeloid and plasmacytoid dendritic cells.
  • Assessment of the role of specific proteases, such as cathepsin S, in epitope generation and destruction.

Main Results:

  • Distinct lysosomal protease signatures were observed in different thymic APC types, suggesting specialized roles in T cell selection.
  • Myeloid dendritic cells demonstrated higher efficiency in autoantigen processing compared to plasmacytoid dendritic cells.
  • Cathepsin S was identified as crucial for processing myelin basic protein and proinsulin, and it destroyed known T cell epitopes.

Conclusions:

  • The differential expression of lysosomal proteases by thymic APC subsets may influence the selection of CD4+ T cells.
  • Cathepsin S activity in thymic dendritic cells can lead to the destruction of self-epitopes, potentially facilitating the escape of autoreactive T cells.
  • Cathepsin S is a significant factor modulating the selection of autoreactive T cells during thymic development.