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Zwitterionic polysaccharides stimulate T cells by MHC class II-dependent interactions
Wiltrud M Kalka-Moll1, Arthur O Tzianabos, Paula W Bryant
1Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. Wiltrud.Kalka-Moll@medizin.uni-koeln.de
Journal of Immunology (Baltimore, Md. : 1950)
|November 22, 2002
Summary
Zwitterionic polysaccharides (ZPSs) from bacteria can activate T cells, challenging previous understanding. This study shows that antigen-presenting cells (APCs) require MHC class II molecules, specifically HLA-DR, to present ZPSs for T cell activation.
Area of Science:
- Immunology
- Microbial Pathogenesis
- Molecular Biology
Background:
- Bacterial polysaccharides are typically T cell-independent antigens.
- Zwitterionic polysaccharides (ZPSs) possess both positive and negative charges, enabling T cell activation.
- Previous understanding excluded cell-mediated immune responses to bacterial polysaccharides.
Purpose of the Study:
- To elucidate the requirements for zwitterionic polysaccharide (ZPS) presentation to CD4(+) T cells.
- To investigate the role of antigen-presenting cells (APCs) and MHC molecules in ZPS-mediated T cell activation.
- To define the mechanism of ZPS interaction with APCs for T cell stimulation.
Main Methods:
- Investigated T cell activation by ZPSs using various APCs (monocytes, dendritic cells, B cells).
- Utilized monoclonal antibodies (mAbs) against MHC class II and class I molecules to block T cell activation.
- Employed immunoprecipitation and electron microscopy to visualize ZPS-APC interactions, focusing on MHC class II and HLA-DR.
Main Results:
- Direct interaction between T cells and APCs is essential for ZPS-induced T cell activation.
- APCs lacking MHC class II molecules do not support ZPS-mediated T cell activation.
- Monoclonal antibody against HLA-DR specifically blocked ZPS-mediated T cell activation, indicating its crucial role.
- Immunoprecipitation and electron microscopy confirmed ZPS binding to HLA-DR on APCs and its colocalization within the endocytic pathway.
Conclusions:
- MHC class II molecules, particularly HLA-DR, on professional APCs are indispensable for ZPS-induced T cell activation.
- The findings suggest that ZPS binding to HLA-DR is a prerequisite for T cell activation.
- This research redefines the immunogenicity of bacterial polysaccharides and their interaction with the adaptive immune system.