title: HLA-DP molecules bind cobalt: a possible explanation for the genetic association with hard metal disease.
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.
authors.affiliation: Department of Cell Biology and Development, University La Sapienza, Rome, Italy.
authors.forename: I
authors.initials: I
authors.lastname: Potolicchio
authors.forename: A
authors.initials: A
authors.lastname: Festucci
authors.forename: P
authors.initials: P
authors.lastname: Hausler
authors.forename: R
authors.initials: R
authors.lastname: Sorrentino
mesh_terms: D017951:Antigen Presentation; D001665:Binding Sites / Q000235:genetics; D002460:Cell Line; D003035:Cobalt / Q000378:metabolism* / Q000633:toxicity*; D003037:Cobalt Radioisotopes; D004391:Dust / Q000009:adverse effects; D014644:Genetic Variation; D006682:HLA-DP Antigens / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D006684:HLA-DR Antigens / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D009784:Occupational Diseases / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D011658:Pulmonary Fibrosis / Q000209:etiology* / Q000235:genetics / Q000378:metabolism
chemical_list: D003037:Cobalt Radioisotopes; D004391:Dust; D006682:HLA-DP Antigens; D006684:HLA-DR Antigens; D003035:Cobalt