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Preparation of Tumor Antigen-loaded Mature Dendritic Cells for Immunotherapy
Published on: August 1, 2013
Apoptotic cells deliver processed antigen to dendritic cells for cross-presentation
Nathalie E Blachère1, Robert B Darnell, Matthew L Albert
1Laboratoire d'Immunobiologie des Cellules Dendritiques, Institut Pasteur, Paris, France.
Plos Biology
|April 21, 2005
Summary
Dendritic cells (DCs) present antigens from apoptotic cells via two pathways. One requires the transporter associated with antigen processing (TAP), while a second, stress-enhanced pathway bypasses TAP by transferring pre-processed antigens from dying cells.
Area of Science:
- Immunology
- Cell Biology
- Antigen Presentation
Background:
- Dendritic cells (DCs) cross-present antigens from apoptotic cells to generate MHC class I/peptide complexes.
- Early recognition and internalization of apoptotic cells by DCs are understood, but antigen processing pathways remain unclear.
Purpose of the Study:
- To elucidate the antigen-processing pathways utilized by dendritic cells (DCs) for cross-presentation of antigens derived from engulfed apoptotic cells.
- To investigate the role of the transporter associated with antigen processing (TAP) in exogenous antigen presentation.
Main Methods:
- Development of a mouse model to assay T cell activation against antigens from apoptotic cells.
- Analysis of antigen trafficking and MHC class I/peptide complex formation in DCs, including TAP-deficient models.
Main Results:
- Two distinct pathways for exogenous antigen trafficking and presentation were identified.
- Pathway 1: Antigen presentation dependent on the DC's functional transporter associated with antigen processing (TAP).
- Pathway 2: Antigen presentation in TAP-deficient DCs, suggesting transfer of pre-processed antigen from dying cells.
Conclusions:
- Dying cells can transfer pre-processed antigens to DCs, enabling MHC class I complex formation independently of TAP.
- The TAP-independent pathway may be more efficient under stress conditions like viral infection.
- Apoptotic cells may pre-select immunologically relevant antigenic determinants for presentation.
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01:17Phagocytosis of Apoptotic Cells
Cells undergoing apoptosis form apoptotic bodies that must be removed immediately to prevent inflammation, autoimmune diseases, and necrosis. Phagocytosis is carried out by professional phagocytes such as macrophages or immature dendritic cells. Non-professional phagocytes such as epithelial cells and fibroblasts also take part in this process; however, they are not as effective as professional phagocytes.
Normal cells contain receptors that prevent them from being recognized by phagocytes.
Normal cells contain receptors that prevent them from being recognized by phagocytes.
01:26Antigens Involved in Adaptive Immunity
An antigen is any substance the immune system identifies as foreign and potentially harmful to the body, prompting an immune response. Antigens have two functional properties: immunogenicity and reactivity. Immunogenicity is the ability of an antigen to stimulate a specific immune response. At the same time, reactivity describes the antigen's ability to react with the cells and antibodies produced in response to it.
Complete Antigens
Complete antigens possess both immunogenicity and reactivity.
Complete Antigens
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01:22Antigen Presenting Cells
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01:31Antigen Processing Pathways
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01:27Cytotoxic T Cells-mediated Immune Response
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