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Purification of the Membrane Compartment for Endoplasmic Reticulum-associated Degradation of Exogenous Antigens in Cross-presentation
Published on: August 21, 2017
Cell surface heparan sulfate proteoglycans influence MHC class II-restricted antigen presentation
Michel Léonetti1, Adeline Gadzinski, Gervaise Moine
1Institut de Biologie et Technologies de Saclay, Service de Pharmacologie et d' Immunoanalyse, and Laboratoire d'Ingénierie des Anticorps pour la Santé, Commissariat à l'Energie Atomique et aux Energies Alternatives, Gif-sur-Yvette, France. michel.leonetti@cea.fr
Journal of Immunology (Baltimore, Md. : 1950)
|September 10, 2010
Summary
Heparan sulfate proteoglycans (HSPGs) act as receptors, enhancing antigen presentation to T cells. Proteins binding HSPGs may elicit a stronger immune response, influencing antigen processing and T cell stimulation.
Area of Science:
- Immunology
- Cell Biology
- Biochemistry
Background:
- Heparan sulfate proteoglycans (HSPGs) are crucial cell surface and extracellular matrix glycoproteins.
- HSPGs modulate protein interactions and influence various biological processes.
- Their role in MHC class II-restricted antigen presentation was previously unclear.
Purpose of the Study:
- To investigate the influence of HSPGs on MHC class II-restricted antigen presentation.
- To determine if HSPGs can act as receptors or coreceptors in antigen processing and presentation.
Main Methods:
- Coupling a heparan sulfate ligand (HIV-1 Tat protein fragment) to a model protein antigen.
- Assessing antigen binding to antigen-presenting cells (APCs).
- Measuring T cell stimulation by modified antigens, with and without heparin or free Tat fragment.
- Investigating immune complexes with FcγRII-bearing APCs.
Main Results:
- Coupling the Tat fragment to antigen increased its cellular binding and T cell stimulation up to 180-fold.
- This boosting effect was dependent on antigen processing and abolished by excess heparin or free Tat fragment.
- HSPGs act as receptors in MHC class II processing and presentation.
- With FcγRII-bearing APCs, HSPG-coupled antigen in immune complexes enhanced T cell stimulation up to 700-fold.
- This FcγRII-mediated effect was abolished by heparin, indicating HSPGs act as coreceptors.
Conclusions:
- Heparan sulfate proteoglycans (HSPGs) significantly influence MHC class II-restricted antigen presentation.
- HSPGs can function as receptors and coreceptors in antigen processing and presentation pathways.
- Proteins with inherent heparan sulfate-binding capacity may be more efficiently supported by the immune system.
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