Chaperones of the class I peptide-loading complex facilitate the constitutive presentation of endogenous antigens on HLA-DP84GGPM87

Mark Anczurowski, Kenji Sugata, Yukiko Matsunaga, Yuki Yamashita, Chung Hsi Wang, Tingxi Guo, Kenji Murata, Hiroshi Saijo, Yuki Kagoya, Kayoko Saso, Marcus O. Butler, Naoto Hirano

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

Recent work has delineated key differences in the antigen processing and presentation mechanisms underlying HLA-DP alleles encoding glycine at position 84 of the DPβ chain (DP84GGPM87). These DPs are unable to associate with the class II-associated Ii peptide (CLIP) region of the invariant chain (Ii) chaperone early in the endocytic pathway, leading to continuous presentation of endogenous antigens. However, little is known about the chaperone support involved in the loading of these endogenous antigens onto DP molecules. Here, we demonstrate the proteasome and TAP dependency of this pathway and reveal the ability of HLA class I to compete with DP84GGPM87 for the presentation of endogenous antigens, suggesting that shared subcellular machinery may exist between the two classes of HLA. We identify physical interactions of prototypical class I-associated chaperones with numerous DP alleles, including TAP2, tapasin, ERp57, calnexin, and calreticulin, using a conventional immunoprecipitation and immunoblot approach and confirm the existence of these interactions in vivo through the use of the BioID2 proximal biotinylation system in human cells. Based on immunological assays, we then demonstrate the ability of each of these chaperones to facilitate the presentation of endogenously derived, but not exogenously derived, antigens on DP molecules. Considering previous genetic and clinical studies linking DP84GGPM87 to disease frequency and severity in autoimmune disease, viral infections, and cancer, we suggest that the above chaperones may form the molecular basis of these observable clinical differences through facilitating the presentation of endogenously derived antigens to CD4+ T cells.

Original languageEnglish
Pages (from-to)114-125
Number of pages12
JournalJournal of Autoimmunity
Volume102
DOIs
Publication statusPublished - 2019 Aug
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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