title: EpsinR, a target for pyrenocine B, role in endogenous MHC-II-restricted antigen presentation.
abstract: While the presentation mechanism of antigenic peptides derived from exogenous proteins by MHC class II molecules is well understood, relatively little is known about the presentation mechanism of endogenous MHC class II-restricted antigens. We therefore screened a chemical library of 200 compounds derived from natural products to identify inhibitors of the presentation of endogenous MHC class II-restricted antigens. We found that pyrenocine B, a compound derived from the fungus Pyrenochaeta terrestris, inhibits presentation of endogenous MHC class II-restricted minor histocompatibility antigen IL-4 inducible gene 1 (IL4I1) by primary dendritic cells (DCs). Phage display screening and surface plasmon resonance (SPR) analysis were used to investigate the mechanism of suppressive action by pyrenocine B. EpsinR, a target molecule for pyrenocine B, mediates endosomal trafficking through binding of soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs). Lentiviral-mediated short hairpin (sh) RNA downregulation of EpsinR expression in DCs resulted in a decrease in the responsiveness of CD4+ T cells. Our data thus suggest that EpsinR plays a role in antigen presentation, which provides insight into the mechanism of presentation pathway of endogenous MHC class II-restricted antigen.
authors.affiliation: Laboratory of Biology, Azabu University School of Veterinary Medicine, Sagamihara, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Shishido
authors.forename: Masami
authors.initials: M
authors.lastname: Hachisuka
authors.forename: Kai
authors.initials: K
authors.lastname: Ryuzaki
authors.forename: Yuko
authors.initials: Y
authors.lastname: Miura
authors.forename: Atsushi
authors.initials: A
authors.lastname: Tanabe
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Tamura
authors.forename: Tomoe
authors.initials: T
authors.lastname: Kusayanagi
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Takeuchi
authors.forename: Shinji
authors.initials: S
authors.lastname: Kamisuki
authors.forename: Fumio
authors.initials: F
authors.lastname: Sugawara
authors.forename: Hiroeki
authors.initials: H
authors.lastname: Sahara
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology*; D000818:Animals; D017951:Antigen Presentation / Q000187:drug effects* / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D061505:Cell Surface Display Techniques; D003713:Dendritic Cells / Q000276:immunology; D005420:Flavoproteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D005656:Fungal Proteins / Q000494:pharmacology; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D050830:L-Amino Acid Oxidase; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D011753:Pyrones / Q000494:pharmacology; D034622:RNA Interference; D034741:RNA, Small Interfering; D050600:SNARE Proteins / Q000276:immunology; D020349:Surface Plasmon Resonance
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; C000595657:EpsinR protein, mouse; D005420:Flavoproteins; D005656:Fungal Proteins; D000949:Histocompatibility Antigens Class II; D011753:Pyrones; D034741:RNA, Small Interfering; D050600:SNARE Proteins; C052580:pyrenocine B; C484538:Il4i1 protein, mouse; D050830:L-Amino Acid Oxidase
keywords: Antigen presentation; Epsin R; MHC class II; Pyrenocine B; SNARE