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Updated: Aug 8, 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

Cytoplasmic processing is a prerequisite for presentation of an endogenous antigen by major histocompatibility

J D Lich1, J F Elliott, J S Blum

  • 1Department of Microbiology and Immunology and the Walther Oncology Center, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA.

The Journal of Experimental Medicine
|May 3, 2000
PubMed

Insights

Major histocompatibility complex (MHC) class II antigen presentation involves distinct processing pathways for exogenous versus cytoplasmic antigens. Cytoplasmic antigen processing for MHC class II presentation relies on proteasomes and calpains.

Area of Science:

  • Immunology
  • Molecular Biology
  • Cellular Biology

Background:

  • Major histocompatibility complex (MHC) class II-restricted presentation of cytoplasmic antigens is known, but the processing mechanisms remain unclear.
  • Understanding antigen processing is crucial for deciphering immune responses and developing targeted therapies.

Purpose of the Study:

  • To investigate the processing pathways of exogenous and endogenous glutamate decarboxylase (GAD) for MHC class II presentation.
  • To identify the key proteases involved in the presentation of cytoplasmic antigens via MHC class II.

Main Methods:

  • Biochemical and functional studies were conducted using human histocompatibility leukocyte antigen (HLA) class II-DR4(+) antigen-presenting cells.
  • Antigen presentation efficiency was assessed for both exogenously introduced and cytoplasmically expressed GAD.
  • The role of endosomal/lysosomal and cytoplasmic proteases (proteasome, calpain) in antigen processing was evaluated.

Main Results:

  • Efficient presentation of GAD epitopes occurred irrespective of exogenous or cytoplasmic delivery, requiring peptide-antigen and newly synthesized MHC class II molecules.
  • Exogenous GAD processing required endosomal/lysosomal acidification and proteases, following the classical pathway.
  • Endogenous GAD processing depended on cytoplasmic proteases, including the proteasome and calpain, necessitating translocation to membrane organelles.

Conclusions:

  • Antigen processing for MHC class II presentation diverges based on delivery route, with cytoplasmic antigens utilizing a distinct pathway involving proteasomes and calpains.
  • Translocation of processed cytoplasmic antigens into membrane organelles is essential for MHC class II presentation.
  • These findings elucidate novel roles for cytoplasmic proteases in MHC class II-restricted antigen presentation.

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