Related Experiment Video

Updated: Jan 9, 2026

Purification of the Membrane Compartment for Endoplasmic Reticulum-associated Degradation of Exogenous Antigens in Cross-presentation
12:48

Purification of the Membrane Compartment for Endoplasmic Reticulum-associated Degradation of Exogenous Antigens in Cross-presentation

Published on: August 21, 2017

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WDFY4-dependent cross-presentation proceeds via a vacuolar antigen-processing route

J Luke Postoak1, Alyssa Koch1, Sicong Shan1

  • 1Department of Pathology and Immunology, Washington University in St. Louis, School of Medicine, 660 S. Euclid Avenue, St. Louis, MO 63110.

Proceedings of the National Academy of Sciences of the United States of America
|December 9, 2025
PubMed

Insights

Cross-presentation by dendritic cells (cDC1) is TAP-dependent, not for antigen processing, but for MHC-I trafficking. This finding challenges existing models of antigen presentation.

Area of Science:

  • Immunology
  • Cell Biology

Background:

  • The mechanism of antigen cross-presentation by type I conventional dendritic cells (cDC1) is debated.
  • One model suggests antigen processing in the cytosol after phagolysosome escape, requiring proteasomal degradation and TAP-dependent ER entry.
  • An alternative model proposes antigen processing within endocytic vesicles.

Purpose of the Study:

  • To investigate the role of the Transporter associated with Antigen Processing (TAP) in cDC1 cross-presentation.
  • To elucidate the intracellular trafficking pathway of MHC class I (MHC-I) molecules during cross-presentation.

Main Methods:

  • Utilized TAP-deficient cDC1 to assess cross-presentation efficiency.
  • Tracked MHC-I molecule trafficking within dendritic cells.

Main Results:

  • Demonstrated that cross-presentation by cDC1 is TAP-dependent.
  • Showed that TAP is crucial for the proper trafficking of MHC-I molecules.
  • Identified a post-Golgi compartment as the site for MHC-I loading during cross-presentation, potentially independent of TAP.

Conclusions:

  • Re-evaluated the role of TAP in cDC1 cross-presentation, shifting focus from antigen processing to MHC-I trafficking.
  • Proposed a model where TAP facilitates MHC-I transport to a specific compartment for loading, independent of antigen peptide supply via TAP.

Keywords:
antigen processingcross-presentationdendritic cells

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