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Related Concept Videos

Multiple Sclerosis l: Introduction01:19

Multiple Sclerosis l: Introduction

Multiple sclerosis is a chronic autoimmune disease of the central nervous system (CNS) that affects the brain, spinal cord, and optic nerves. It is an inflammatory demyelinating disorder and a leading cause of neurological disability in young adults.EpidemiologyMS commonly begins between 20 and 40 years of age and is twice as common in women. Its exact cause remains unclear, but genetic susceptibility contributes, with higher risk in first-degree relatives and identical twins. A greater...
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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...

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Multiple sclerosis: T-cell receptor expression in distinct brain regions.

Andreas Junker1, Jana Ivanidze, Joachim Malotka

  • 1Institute for Clinical Neuroimmunology, Ludwig Maximilians University, D-81377 Munich, Germany.

Brain : a Journal of Neurology
|September 25, 2007
PubMed
Summary

In multiple sclerosis (MS) patients, identical T-cell clones were found across distinct brain regions, including lesions and normal-appearing white matter. These pervasive T-cell clones are unique to each patient, suggesting a widespread immune response in MS.

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Published on: November 17, 2020

Area of Science:

  • Neuroimmunology
  • Immunogenetics
  • Molecular Medicine

Background:

  • Multiple sclerosis (MS) is an inflammatory autoimmune disease affecting the central nervous system.
  • T-cell clones are known to expand in MS lesions, but their distribution across different brain areas remains unclear.
  • Understanding T-cell clonality in MS is crucial for elucidating disease mechanisms.

Purpose of the Study:

  • To investigate the presence and distribution of T-cell receptor (TCR) repertoires in distinct anatomical regions of the MS brain.
  • To determine if identical T-cell clones infiltrate both MS lesions and normal-appearing white matter (NAWM).
  • To explore the clonal relationship and potential antigen-driven selection of T cells in MS.

Main Methods:

  • Analysis of TCR beta-chain CDR3 spectratyping in 19 MS lesions and 5 NAWM regions from four post-mortem brains.
  • Sequencing of approximately 800 Vbeta-NDN-Jbeta combinations per anatomical site.
  • Laser microdissection of CD8+ T cells followed by single-cell PCR to characterize TCRs of pervasive clones.

Main Results:

  • Identical T-cell clones were detected in multiple, anatomically distinct regions within individual MS patients.
  • These pervasive clones were found in both MS lesions and NAWM, indicating widespread infiltration.
  • Some T-cell clones were present in up to nine different sites within a single patient, and none were shared between patients.
  • Silent nucleotide exchanges in the NDN region suggest antigen-driven selection.
  • At least some pervasive clones were identified within the CD8+ T-cell subset.

Conclusions:

  • Widespread, patient-specific T-cell clones are present throughout the MS brain, affecting both lesions and normal-appearing white matter.
  • The presence of identical clones in diverse locations suggests a systemic rather than purely localized immune response in MS.
  • The findings highlight the pathogenic relevance of CD8+ T cells and suggest antigen-driven clonal expansion in MS pathogenesis.