HLA-DP molecules bind cobalt: a possible explanation for the genetic association with hard metal disease

Détails

ID Serval
serval:BIB_9CC6A32722A2
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
HLA-DP molecules bind cobalt: a possible explanation for the genetic association with hard metal disease
Périodique
European Journal of Immunology
Auteur⸱e⸱s
Potolicchio  I., Festucci  A., Hausler  P., Sorrentino  R.
ISSN
0014-2980 (Print)
Statut éditorial
Publié
Date de publication
07/1999
Volume
29
Numéro
7
Pages
2140-7
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Jul
Résumé
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.
Mots-clé
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
Création de la notice
25/01/2008 16:16
Dernière modification de la notice
20/08/2019 16:03
Données d'usage