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Post-translational Translocation of Proteins to the RER01:27

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Base complementarity between the three base pairs of mRNA codon and the tRNA anticodon is not a failsafe mechanism. Inaccuracies can range from a single mismatch to no correct base pairing at all. The free energy difference between the correct and nearly correct base pairs can be as small as 3 kcal/ mol. With complementarity being the only proofreading step, the estimated error frequency would be one wrong amino acid in every 100 amino acids incorporated. However, error frequencies observed in...
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Related Experiment Video

Updated: Feb 15, 2026

Detection of Post-translational Modifications on Native Intact Nucleosomes by ELISA
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T cells specific for post-translational modifications escape intrathymic tolerance induction.

Bruno Raposo1,2, Patrick Merky1, Christina Lundqvist3

  • 1Section for Medical Inflammation Research, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Scheeles väg 2, 17177, Stockholm, Sweden.

Nature Communications
|January 26, 2018
PubMed
Summary

Central tolerance is crucial for preventing autoimmunity. This study reveals that T cells targeting post-translationally modified (PTM) self-antigens, like collagen type II, can escape thymic selection, potentially leading to autoimmune diseases.

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Area of Science:

  • Immunology
  • Autoimmunity
  • Molecular Biology

Background:

  • Effective central tolerance relies on thymic expression of tissue-restricted antigens.
  • The tolerance induction for post-translationally modified (PTM) self-antigens remains unclear.

Purpose of the Study:

  • To investigate whether central tolerance extends to PTM self-antigens.
  • To elucidate the mechanism by which PTM self-antigens might evade thymic selection.

Main Methods:

  • Utilized a mouse model of autoimmunity dependent on PTM of collagen type II.
  • Analyzed T cell responses to both non-modified and PTM variants of collagen type II.
  • Assessed thymic selection and peripheral T cell populations.

Main Results:

  • T cells specific for non-modified collagen type II underwent efficient central tolerance.
  • T cells reactive to the PTM variant of collagen type II escaped thymic selection.
  • The PTM variant was the dominant form in the periphery but absent or at low levels in the thymus.

Conclusions:

  • PTM self-antigens may escape central tolerance induction due to insufficient thymic presentation.
  • This mechanism could explain autoimmune diseases targeting PTM self-antigens.
  • A significant portion of self-antigens are PTM, suggesting broad implications for immune tolerance.