| RRC ID |
54899
|
| 著者 |
Yorifuji H, Arase N, Kohyama M, Hirano T, Suenaga T, Kumanogoh A, Arase H.
|
| タイトル |
Transport of cellular misfolded proteins to the cell surface by HLA-B27 free heavy chain.
|
| ジャーナル |
Biochem Biophys Res Commun
|
| Abstract |
HLA class I molecules play a central role in the immune system by presenting peptide antigens to cytotoxic T cells. Although most HLA class I molecules are associated with β2-microglobulin, HLA class I heavy chain that is not associated with β2-microglobulin is also expressed on certain cells. We recently found that cellular misfolded proteins are transported to the cell surface by HLA class II molecules via association with their peptide-binding grooves. Furthermore, misfolded self-antigens bound to autoimmune disease-susceptible HLA class II molecules are the targets for autoantibodies produced in certain autoimmune diseases. In the present study, we found that misfolded proteins were also transported to the cell surface by specific HLA class I molecules including HLA-B27, which is strongly associated with ankylosing spondylitis. In addition, the efficiency with which HLA class I molecules encoded by each allele transport misfolded proteins to the cell surface was significantly correlated with HLA class I free heavy chain expression on that surface. Moreover, misfolded proteins were coprecipitated with HLA class I free heavy chain but not with correctly folded HLA class I molecules. These findings reveal a novel function of HLA class I molecules to transport misfolded proteins to the cell surface, which might help us to understand the pathogenesis of HLA class I-associated diseases.
|
| 巻・号 |
511(4)
|
| ページ |
862-868
|
| 公開日 |
2019-4-16
|
| DOI |
10.1016/j.bbrc.2019.02.120
|
| PII |
S0006-291X(19)30321-3
|
| PMID |
30850159
|
| MeSH |
Animals
Chickens
HEK293 Cells
HLA-B27 Antigen / metabolism*
Humans
Muramidase / metabolism
Protein Folding
Protein Transport
Proteostasis
Proteostasis Deficiencies / metabolism*
Spondylitis, Ankylosing / metabolism*
beta 2-Microglobulin / metabolism
|
| IF |
2.705
|
| 引用数 |
0
|
| リソース情報 |
| ヒト・動物細胞 |
293T(RCB2202) |
