Involvement of cathepsin E in exogenous antigen processing in primary cultured murine microglia

Tsuyoshi Nishioku, Koichi Hashimoto, Keizo Yamashita, Shyh Yuh Liou, Yoshifumi Kagamiishi, Hitoshi Maegawa, Nobuo Katsube, Christoph Peters, Kurt Von Figura, Paul Saftig, Nobuhiko Katunuma, Kenji Yamamoto, Hiroshi Nakanishi

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Abstract

We have attempted to elucidate an involvement of cathepsin E (CE) in major histocompatibility complex class II-mediated antigen presentation by microglia. In primary cultured murine microglia, CE was localized mainly in early endosomes and its expression level was markedly increased upon stimulation with interferon-γ. Pepstatin A, a specific inhibitor of aspartic proteases, significantly inhibited interleukin-2 production from an OVA-(266-281)-specific T helper cell hybridomas upon stimulation with native OVA presented by interferon-γ-treated microglia. However, pepstatin A failed to inhibit the presentation of OVA-(266-281) peptide. The possible involvement of CE in the processing of native OVA into antigenic peptide was further substantiated by that digested fragments of native OVA by CE could be recognized by OVA-specific Th cells. Cathepsin D also degraded native OVA into antigenic peptide, whereas microglia prepared from cathepsin D-deficient mice retained an ability for antigen presentation. On the other hand, the requirement for cysteine proteases such as cathepsins S and B in the processing of invariant chain (Ii) was confirmed by immunoblot analyses in the presence of their specific inhibitors. In conclusion, CE is required for the generation of an antigenic epitope from OVA but not for the processing of Ii in microglia.

Original languageEnglish
Pages (from-to)4816-4822
Number of pages7
JournalJournal of Biological Chemistry
Volume277
Issue number7
DOIs
Publication statusPublished - Feb 15 2002

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Nishioku, T., Hashimoto, K., Yamashita, K., Liou, S. Y., Kagamiishi, Y., Maegawa, H., Katsube, N., Peters, C., Von Figura, K., Saftig, P., Katunuma, N., Yamamoto, K., & Nakanishi, H. (2002). Involvement of cathepsin E in exogenous antigen processing in primary cultured murine microglia. Journal of Biological Chemistry, 277(7), 4816-4822. https://doi.org/10.1074/jbc.M108382200