In vivo requirement for Atg5 in antigen presentation by dendritic cells
Open accessAbstract
Autophagy is known to be important in presentation of cytosolic antigens on MHC class II (MHC II). However, the role of autophagic process in antigen presentation in vivo is unclear. Mice with dendritic cell (DC)-conditional deletion in Atg5, a key autophagy gene, showed impaired CD4(+) T cell priming after herpes simplex virus infection and succumbed to rapid disease. The most pronounced defect of Atg5(-/-) DCs was the processing and presentation of phagocytosed antigens containing Toll-like receptor stimuli for MHC class II. In contrast, cross-presentation of peptides on MHC I was intact in the absence of Atg5. Although induction of metabolic autophagy did not enhance MHC II presentation, autophagic machinery was required for optimal phagosome-to-lysosome fusion and subsequent processing of antigen for MHC II loading. Thus, our study revealed that DCs utilize autophagic machinery to optimally process and present extracellular microbial antigens for MHC II presentation.
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Fusion of the lysosome to the phagosome in dendritic cells requires Atg5 and LC3 for efficient antigen degradation and presentation to T cells.
“In a similar manner fusion of the lysosome to the phagosome in dendritic cells required Atg5 and LC3 for efficient antigen degradation and presentation to T cells (Lee et al., 2010).”
From Noncanonical autophagy promotes the visual cycle (2013) · cites this paper as Lee et al., 2010
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- Authors
- Lee, H. K., Mattei, L. M., Steinberg, B. E., Alberts, P., Lee, Y. H., Chervonsky, A., Mizushima, N., Grinstein, S., & Iwasaki, A.
- Affiliations
- Yale University (US)
- University of Toronto (CA)
- University of Chicago (US)
- Tokyo Medical and Dental University (JP)
- Corresponding author
- Iwasaki, Akiko
- ORCID
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2010-02
- Volume
- 32
- Issue
- 2
- Pages
- 227-239
- ISSN
- 1074-7613 (ISSN-L)
- PMC
- PMC2996467
- OpenAlex
- W1992881494
- Cited by
- 506
- References
- 61
- Citations by year
- 2026: 15 · 2025: 12 · 2024: 23 · 2023: 28 · 2022: 27 · 2021: 28 · 2020: 32 · 2019: 32 · 2018: 26 · 2017: 35 · 2016: 40 · 2015: 35 · 2014: 33 · 2013: 45 · 2012: 39
- FWCI
- 32.44
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Immunity (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- KAIST Institutional Repository (KAIST) (submittedVersion)
- Funders
- National Institute of Allergy and Infectious Diseases (R01AI064705, AI062428, AI054359, AI 064705, R01AI062428, AI72627, R56AI062428, R01AI054359, R01AI081884, R01AI072627)
- Topics
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- ATG5, autophagy, dendritic cells, antigen presentation, MHC class II, CD4+ T cell priming, herpes simplex, Toll-like receptors, cross-presentation
- MeSH terms
- Autophagy-Related Protein 5, Animals, Histocompatibility Antigens Class II, Cells, Cultured, Dendritic Cells, Female, Herpes Simplex, Lymphocyte Activation, Mice, Inbred C57BL, Microtubule-Associated Proteins, Radiation Chimera, Antigen Presentation, Herpesvirus 2, Human, Mice, Knockout, RNA, Small Interfering, Mice
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