EpsinR,a target for pyrenocine B,role in endogenous MHC‐II‐restricted antigen presentation |
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| Authors: | Tatsuya Shishido Masami Hachisuka Kai Ryuzaki Yuko Miura Atsushi Tanabe Yasuaki Tamura Tomoe Kusayanagi Toshifumi Takeuchi Shinji Kamisuki Fumio Sugawara Hiroeki Sahara |
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| Affiliation: | 1. Laboratory of Biology, Azabu University School of Veterinary Medicine, Sagamihara, Japan;2. Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan;3. Genome and Drug Research Center, Tokyo University of Science, Chiba, Japan |
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| 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. |
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| Keywords: | Antigen presentation Epsin R MHC class II Pyrenocine B SNARE |
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