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Updated: Aug 19, 2026

Immunopeptidomics: Isolation of Mouse and Human MHC Class I- and II-Associated Peptides for Mass Spectrometry Analysis
09:32

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

Published on: October 15, 2021

Spatial separation of HLA-DM/HLA-DR interactions within MIIC and phagosome-induced immune escape

Wilbert Zwart1, Alexander Griekspoor, Coenraad Kuijl

  • 1Division of Tumor Biology , Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.

Immunity
|February 23, 2005
PubMed

Insights

Major Histocompatibility Complex (MHC) class II molecules, like Human Leukocyte Antigen (HLA)-DR, are crucial for presenting antigens. This study reveals HLA-DR and HLA-DM interactions are absent in Salmonella-infected phagosomes, hindering antigen presentation and immune evasion.

Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • Major Histocompatibility Complex (MHC) class II molecules present peptides from endocytic pathways.
  • Human Leukocyte Antigen (HLA)-DR targets MHC class II-containing Compartments (MIIC) for peptide loading.
  • HLA-DM stabilizes HLA-DR during critical peptide exchange.

Purpose of the Study:

  • To visualize HLA-DR and HLA-DM interactions in living cells using FRET.
  • To investigate the impact of Salmonella infection on MHC class II antigen loading.
  • To understand the mechanisms of immune evasion by pathogens.

Main Methods:

  • Generated cells expressing fluorescently tagged HLA-DR (CFP) and HLA-DM (YFP).
  • Utilized Fluorescence Resonance Energy Transfer (FRET) to detect molecular interactions.
  • Employing a cellular model of Salmonella infection to study phagosome function.

Main Results:

  • Observed pH-insensitive HLA-DR/HLA-DM interactions within internal MIIC structures.
  • Found no HLA-DR/HLA-DM interaction at the limiting membrane of MIIC.
  • Demonstrated absence of HLA-DR/HLA-DM interaction and antigen loading in Salmonella-induced phagosomes.

Conclusions:

  • The lack of HLA-DR/HLA-DM interaction at the phagosome membrane prevents antigen loading.
  • Salmonella may evade immune detection by inhibiting MHC class II antigen presentation.
  • Targeting these interactions could offer novel therapeutic strategies.

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