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Updated: Apr 18, 2026

Immunopeptidomics: Isolation of Mouse and Human MHC Class I- and II-Associated Peptides for Mass Spectrometry Analysis
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Immunopeptidomics: Isolation of Mouse and Human MHC Class I- and II-Associated Peptides for Mass Spectrometry Analysis

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Single-molecule motions of MHC class II rely on bound peptides

Haruo Kozono1, Yufuku Matsushita2, Naoki Ogawa3

  • 1CREST Sasaki Team, Japan Science and Technology Agency, Graduate School of Frontier Sciences, The University of Tokyo, Chiba, Japan; Research Institute for Biomedical Sciences, Tokyo University of Science, Chiba, Japan.

Biophysical Journal
|January 22, 2015
PubMed

Insights

Peptide-flanking residues (PFRs) influence how major histocompatibility complex (MHC) molecules bind peptides. Without PFRs, peptides exhibit greater motion, allowing diverse structures for T cell receptor recognition.

Area of Science:

  • Immunology
  • Structural Biology
  • Biophysics

Background:

  • Major histocompatibility complex (MHC) class II proteins bind peptides, influencing T cell receptor (TCR) recognition.
  • Peptide-flanking residues (PFRs) affect peptide binding affinity and immunogenicity, but the underlying mechanisms are unclear.
  • Molecular flexibility of peptide/MHC complexes may dictate TCR recognition.

Purpose of the Study:

  • To investigate the role of PFRs in peptide/MHC dynamics and structure.
  • To elucidate the mechanisms by which PFRs modulate peptide/MHC interactions and immunogenicity.

Main Methods:

  • Single-molecule diffracted x-ray tracking (DXT) to monitor real-time Brownian motion of peptide/MHC complexes.
  • Fluorescence anisotropy to assess molecular motions on the nanosecond timescale.

Main Results:

  • DXT revealed that peptides lacking PFRs exhibit larger rotational motions compared to peptides with PFRs.
  • Fluorescence anisotropy confirmed increased motions for peptides without PFRs on the nanosecond timescale.
  • These findings indicate dynamic peptide motions within the MHC groove.

Conclusions:

  • Peptides without PFRs undergo significant dynamic motions within the MHC groove.
  • This enhanced flexibility allows peptides to adopt diverse structures, potentially influencing TCR recognition.
  • Molecular dynamics of peptide/MHC complexes are critical for immune recognition.

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