Abrogation of self-tolerance by misfolded self-antigens complexed with MHC class II molecules

Hui Jin, Kazuki Kishida, Noriko Arase, Sumiko Matsuoka, Wataru Nakai, Masako Kohyama, Tadahiro Suenaga, Ken Yamamoto, Takehiko Sasazuki, Hisashi Arase

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1 Citation (Scopus)

Abstract

Specific MHC class II alleles are strongly associated with susceptibility to various autoimmune diseases. Although the primary function of MHC class II molecules is to present peptides to helper T cells, MHC class II molecules also function like a chaperone to transport misfolded intracellular proteins to the cell surface. In this study, we found that autoantibodies in patients with Graves' disease preferentially recognize thyroid-stimulating hormone receptor (TSHR) complexed with MHC class II molecules of Graves' disease risk alleles, suggesting that the aberrant TSHR transported by MHC class II molecules is the target of autoantibodies produced in Graves' disease. Mice injected with cells expressing mouse TSHR complexed with MHC class II molecules, but not TSHR alone, produced anti-TSHR autoantibodies. These findings suggested that aberrant self-antigens transported by MHC class II molecules exhibit antigenic properties that differ from normal self-antigens and abrogate self-tolerance, providing a novel mechanism for autoimmunity.

Original languageEnglish
Article numbereabj9867
JournalScience Advances
Volume8
Issue number9
DOIs
Publication statusPublished - Mar 2022

All Science Journal Classification (ASJC) codes

  • General

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