HLA-DP84Gly constitutively presents endogenous peptides generated by the class I antigen processing pathway

Yuki Yamashita, Mark Anczurowski, Munehide Nakatsugawa, Makito Tanaka, Yuki Kagoya, Ankit Sinha, Kenji Chamoto, Toshiki Ochi, Tingxi Guo, Kayoko Saso, Marcus O. Butler, Mark D. Minden, Thomas Kislinger, Naoto Hirano

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11 Citations (Scopus)

Abstract

Classical antigen processing leads to the presentation of antigenic peptides derived from endogenous and exogenous sources for MHC class I and class II molecules, respectively. Here we show that, unlike other class II molecules, prevalent HLA-DP molecules with β-chains encoding Gly84 (DP84Gly) constitutively present endogenous peptides. DP84Gly does not bind invariant chain (Ii) via the class II-associated invariant chain peptide (CLIP) region, nor does it present CLIP. However, Ii does facilitate the transport of DP84Gly from the endoplasmic reticulum (ER) to the endosomal/lysosomal pathway by transiently binding DP84Gly via a non-CLIP region(s) in a pH-sensitive manner. Accordingly, like class I, DP84Gly constitutively presents endogenous peptides processed by the proteasome and transported to the ER by the transporter associated with antigen processing (TAP). Therefore, DP84Gly, found only in common chimpanzees and humans, uniquely uses both class I and II antigenprocessing pathways to present peptides derived from intracellular and extracellular sources.

Original languageEnglish
Article number15244
JournalNature Communications
Volume8
DOIs
Publication statusPublished - 01-01-2017
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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    Yamashita, Y., Anczurowski, M., Nakatsugawa, M., Tanaka, M., Kagoya, Y., Sinha, A., Chamoto, K., Ochi, T., Guo, T., Saso, K., Butler, M. O., Minden, M. D., Kislinger, T., & Hirano, N. (2017). HLA-DP84Gly constitutively presents endogenous peptides generated by the class I antigen processing pathway. Nature Communications, 8, [15244]. https://doi.org/10.1038/ncomms15244