Related Experiment Video

Updated: Jul 27, 2025

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

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Recent progress in type 1 classical dendritic cell cross-presentation - cytosolic, vacuolar, or both?

Ray A Ohara1, Kenneth M Murphy1

  • 1Department of Pathology and Immunology, Washington University in St. Louis, School of Medicine, St. Louis, MO 63110, USA.

Current Opinion in Immunology
|June 5, 2023
PubMed

Insights

Type 1 classical dendritic cells (cDC1s) are key for cross-presentation (XP) of cell-associated antigens. The exact antigen-processing pathway and the role of WD repeat- and FYVE domain-containing protein 4 (WDFY4) in XP remain unclear.

Area of Science:

  • Immunology
  • Cell Biology
  • Antigen Presentation

Background:

  • Type 1 classical dendritic cells (cDC1s) are crucial for cross-presentation (XP) of cell-associated antigens in vivo.
  • The precise mechanisms governing antigen processing within cDC1s for XP are not fully understood.
  • Two models, vacuolar and cytosolic pathways, compete to explain in vivo XP of cell-associated antigens.

Purpose of the Study:

  • To review the current understanding of antigen-processing pathways in cDC1s for cross-presentation.
  • To discuss the role of WD repeat- and FYVE domain-containing protein 4 (WDFY4) in XP.
  • To highlight areas requiring future investigation regarding cDC1 antigen processing and WDFY4 function.

Main Methods:

  • Literature review of existing models for in vivo cross-presentation.
  • Analysis of proposed mechanisms involving vacuolar and cytosolic pathways.
  • Examination of the necessity of WDFY4 in cross-presentation of cell-associated antigens.

Main Results:

  • The exact antigen-processing pathway utilized by cDC1s for XP remains elusive.
  • WD repeat- and FYVE domain-containing protein 4 (WDFY4) is essential for in vivo XP of cell-associated antigens.
  • The specific cellular mechanism of WDFY4 action and its pathway preference (vacuolar vs. cytosolic) are unknown.

Conclusions:

  • Further research is needed to elucidate the antigen-processing pathway in cDC1s.
  • Understanding WDFY4's mechanism is critical for comprehending cDC1-mediated cross-presentation.
  • Resolving these questions will advance knowledge of adaptive immune responses.

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