HLA-DP molecules bind cobalt: a possible explanation for the genetic association with hard metal disease
Details
Serval ID
serval:BIB_9CC6A32722A2
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
HLA-DP molecules bind cobalt: a possible explanation for the genetic association with hard metal disease
Journal
European Journal of Immunology
ISSN
0014-2980 (Print)
Publication state
Published
Issued date
07/1999
Volume
29
Number
7
Pages
2140-7
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Jul
Research Support, Non-U.S. Gov't --- Old month value: Jul
Abstract
Metal dust inhalation induces an interstitial lung disease which may progress to pulmonary fibrosis (hard metal disease, HMD). Cobalt is believed to be the pathogenic agent of HMD. A strong genetic association of HMD with some HLA-DP alleles has been reported although the role of these molecules in the occurrence of the fibrotic disorder remains unclear. A possible explanation of these findings is that HLA-DP but not other HLA class II molecules can bind cobalt. This could have as a consequence an HLA-DP-mediated specific activation of the immune system. To test this hypothesis, we have set up an in vitro binding assay using 57Co and purified HLA-DP and -DR molecules. The results indicate that HLA-DP but not HLA-DR molecules bind cobalt. Moreover, the presence of HLA-DP Glu beta69, which is associated with susceptibility to HMD, determines a higher metal uptake. Molecular modelling of HLA-DP2 molecules places the Glu beta69 residue in a position relevant in determining peptide specificity. The possibility that binding of cobalt by HLA-DP molecules can interfere with their antigen presenting functions is discussed.
Keywords
Antigen Presentation
Binding Sites/genetics
Cell Line
Cobalt/*metabolism/*toxicity
Cobalt Radioisotopes
Dust/adverse effects
HLA-DP Antigens/chemistry/*genetics/*metabolism
HLA-DR Antigens/metabolism
Humans
Models, Molecular
Occupational Diseases/etiology/genetics/metabolism
Protein Binding
Protein Conformation
Pulmonary Fibrosis/*etiology/genetics/metabolism
Variation (Genetics)
Pubmed
Create date
25/01/2008 15:16
Last modification date
20/08/2019 15:03