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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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Antigen receptors are essential components of the immune system crucial in defending the body against foreign invaders. These receptors are present on the surface of B and T cells, enabling them to recognize antigens and mount an appropriate immune response.
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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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Mannosylated glycans impair normal T-cell development by reprogramming commitment and repertoire diversity.

Manuel M Vicente1,2,3, Inês Alves1, Ângela Fernandes1

  • 1i3S - Institute for Research and Innovation in Health, University of Porto, Porto, Portugal.

Cellular & Molecular Immunology
|June 21, 2023
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Summary

Altered T-cell glycosylation, specifically high-mannose structures, disrupts T-cell development and regulatory T-cell generation. This leads to increased susceptibility to inflammation and infection, highlighting the critical role of N-glycans in immune health.

Keywords:
GlycocalyxInflammationN-glycosylationT-cell developmentThymocytes

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Area of Science:

  • Immunology
  • Glycobiology
  • Cellular Biology

Background:

  • T-cell development is crucial for adaptive immunity, involving T-cell receptor (TCR) selection.
  • Glycosylation, a key posttranslational modification, influences protein function, including TCRs.
  • The precise role of glycans in T-cell development beyond TCR selection and disease susceptibility remains largely unknown.

Purpose of the Study:

  • To investigate the stage-specific glycome composition during T-cell development in thymocytes.
  • To determine how altered N-glycosylation impacts T-cell development and immune function.
  • To explore the link between thymocyte glycosylation and susceptibility to inflammatory diseases.

Main Methods:

  • Utilized glycoengineered mice (Rag1CreMgat1fl/fl and Rag1CreMgat2fl/fl) to manipulate N-glycosylation profiles in thymocytes.
  • Analyzed T-cell development checkpoints, including ß-selection, regulatory T-cell generation, and γδT-cell development.
  • Assessed susceptibility to colon and kidney inflammation and infection in mice with altered glycosylation.

Main Results:

  • Discovered dynamic, stage-specific changes in glycome composition during T-cell development.
  • Restricting N-glycosylation to high-mannose structures in thymocytes caused significant defects in T-cell development.
  • A single N-glycan antenna was found to be essential for normal T-cell development, with its absence leading to dysregulation.
  • Mice with altered glycosylation exhibited increased susceptibility to inflammatory conditions and infections.

Conclusions:

  • Mannosylated thymocytes result in dysregulated T-cell development.
  • Altered T-cell glycosylation is directly linked to increased susceptibility to inflammation and infection.
  • N-glycans play a critical, previously unappreciated role in maintaining T-cell homeostasis and preventing disease.