Cited by 506Autophagy in Disease and TherapyImmunotherapy and Immune ResponsesT-cell and B-cell Immunology

In vivo requirement for Atg5 in antigen presentation by dendritic cells

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Lee, Heung Kyu, Mattei, Lisa M., Steinberg, Benjamin E., Alberts, Philipp, Lee, Yun Hee, Chervonsky, Alexander, Mizushima, Noboru, Grinstein, Sergio +1 more·2010·Immunity

Abstract

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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Crossref · 10.1016/j.immuni.2009.12.006

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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
Venue
Immunity
Publisher
Elsevier BV
Published
2010-02
Volume
32
Issue
2
Pages
227-239
ISSN
1074-7613 (ISSN-L)
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
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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