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Control of cross-presentation during dendritic cell maturation.
Beatriz C Gil-Torregrosa1, Ana Maria Lennon-Duménil, Benedikt Kessler
1U520 INSERM, Institut Curie, Paris, France.
European Journal of Immunology
|February 10, 2004
Summary
Dendritic cells (DCs) regulate cross-presentation of antigens. This process is enhanced early in DC maturation but inhibited in fully mature cells due to controlled antigen uptake and transport.
Area of Science:
- Immunology
- Cell Biology
Background:
- Cross-presentation is crucial for initiating cytotoxic T cell responses.
- Dendritic cells (DCs) efficiently cross-present internalized antigens via MHC class I.
- FcgammaR-mediated antigen uptake is a key pathway for cross-presentation in DCs.
Purpose of the Study:
- To investigate the regulation of FcgammaR-mediated cross-presentation during dendritic cell (DC) maturation.
- To elucidate the mechanisms controlling antigen processing and presentation in DCs at different maturation stages.
Main Methods:
- Utilized lipopolysaccharide (LPS) to induce DC maturation.
- Assessed antigen internalization, cytosolic delivery, proteasome activity, and transporter associated with antigen processing (TAP) function.
- Analyzed MHC class I-restricted antigen presentation to CD8(+) T lymphocytes.
Main Results:
- FcgammaR-mediated cross-presentation initially increased post-LPS activation.
- Fully mature DCs exhibited inhibited cross-presentation.
- This inhibition was linked to reduced antigen internalization and cytosolic delivery, despite increased proteasome and TAP activity.
Conclusions:
- FcgammaR-mediated cross-presentation is tightly regulated during DC maturation.
- Maturation involves selective control of antigen uptake and transport to the cytosol.
- This regulation fine-tunes the initiation of cytotoxic immune responses.