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The role of intracellular acidification in antigen processing
1Laboratory of Cellular and Molecular Immunology, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892.
Immunological Reviews
|December 1, 1988
Summary
Intracellular acidic organelles, like early endosomes, are crucial for processing foreign antigens. Impaired acidification in these compartments reduces antigen processing, highlighting their role in immune responses.
Area of Science:
- Immunology
- Cell Biology
Background:
- Intracellular acidic organelles play a role in antigen processing.
- The specific contribution of early endosomes to this process requires further elucidation.
Purpose of the Study:
- To investigate the role of intracellular acidic organelles in foreign antigen processing.
- To determine the specific contribution of early endosomes to antigen processing pathways.
Main Methods:
- Utilized T-cell hybridoma stimulation assays with antigen and cathepsin L precursor.
- Employed Chinese Hamster Ovary (CHO) cells with temperature-sensitive defects in endosomal acidification.
- Transfected cells with MHC class II genes to function as antigen-presenting cells (APCs) for CD4+ T cells.
Main Results:
- Simultaneous addition of antigen and inactive cathepsin L precursor diminished T-cell hybridoma stimulation, indicating impaired antigen processing.
- Uptake of cathepsin L via mannose-6-PO4 receptors was required for this effect.
- CHO cells with defective endosomal acidification showed impaired antigen processing, but not peptide presentation or antigen uptake/degradation.
- This impairment was partially reversed by chloroquine, suggesting a role for acidified early endosomes.
Conclusions:
- Foreign antigens move into an acidic environment during processing.
- Acidified early endosomes contribute to the antigen processing pathway.
- Other acidic compartments are also likely involved in antigen processing.