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In vivo requirement for autophagy in antigen presentation by dendritic cells
Author(s) -
LEE HEUNG KYU,
Lee Yun Hee,
Chervonsky Alexander,
Mizushima Noboru,
Iwasaki Akiko
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1068.13
Subject(s) - atg5 , antigen presentation , microbiology and biotechnology , antigen processing , antigen , autophagy , major histocompatibility complex , antigen presenting cell , t cell , biology , mhc class i , dendritic cell , cross presentation , mhc class ii , chemistry , immune system , immunology , biochemistry , apoptosis
CD4 T cells recognize peptides loaded in the context of class II major histocompatibility complex (MHC). Classically, the peptides found on MHC II complex are generated in the acidified endocytic vesicles upon degradation of antigens derived from intracellular vesicles and extracellular sources. Recent evidence from in vitro experiments indicates that certain cytosolic antigens could also be loaded onto MHC II molecules following autophagy. However, the role of autophagy in antigen presentation in vivo is unknown. Here we examined the in vivo requirement of autophagy in antigen presentation to CD4 T cells using mice deficient in a key component of autophagosome, Atg5. Dendritic cell's ability to induce CD4 T cell responses was measured in Atg5 −/− → WT fetal liver chimeric mice and in CD11c‐Cre‐Atg flox/flox conditional knockout mice in which DCs lack Atg5. Despite their intact ability to capture antigens, migrate, mature and produce cytokines, Atg5‐deficient dendritic cells (DCs) were impaired in their capacity to process and present certain forms of antigens to CD4 T cells. These results revealed a critical in vivo requirement for autophagy in processing and presentation of antigens for MHC II by DCs, leading to the activation of CD4 T cell responses.