Linked Life Data

15067095

Source:http://linkedlifedata.com/resource/pubmed/id/15067095

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2004-4-6
pubmed:abstractText
To test the hypothesis that HLA-B27 predisposes to disease by forming disulfide-linked homodimers, we examined rats transgenic for HLA-B27, mutant Cys(67)Ser HLA-B27, or HLA-B7. In splenic Con A blasts from high transgene copy B27 lines that develop inflammatory disease, the anti-H chain mAb HC10 precipitated four bands of molecular mass 78-105 kDa and additional higher molecular mass material, seen by nonreducing SDS-PAGE. Upon reduction, all except one 78-kDa band resolved to 44 kDa, the size of the H chain monomer. The 78-kDa band was found to be BiP/Grp78, and the other high molecular mass material was identified as B27 H chain. Analysis of a disease-resistant low copy B27 line showed qualitatively similar high molecular mass bands that were less abundant relative to H chain monomer. Disease-prone rats with a Cys(67)Ser B27 mutant showed B27 H chain bands at 95 and 115 kDa and a BiP band at 78 kDa, whereas only scant high molecular mass bands were found in cells from control HLA-B7 rats. (125)I-surface labeled B27 oligomers were immunoprecipitated with HC10, but not with a mAb to folded B27-beta(2)-microglobulin-peptide complexes. Immunoprecipitation of BiP with anti-BiP Abs coprecipitated B27 H chain multimers. Folding and maturation of B27 were slow compared with B7. These data indicate that disulfide-linked intracellular H chain complexes are more prone to form and bind BiP in disease-prone wild-type B27 and B27-C67S rats than in disease-resistant HLA-B7 rats. The data support the hypothesis that accumulation of misfolded B27 participates in the pathogenesis of B27-associated disease.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
172
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5110-9
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:15067095-Animals, pubmed-meshheading:15067095-Animals, Genetically Modified, pubmed-meshheading:15067095-Antibodies, Monoclonal, pubmed-meshheading:15067095-Binding Sites, Antibody, pubmed-meshheading:15067095-Carrier Proteins, pubmed-meshheading:15067095-Disulfides, pubmed-meshheading:15067095-Endoplasmic Reticulum, pubmed-meshheading:15067095-HLA-B27 Antigen, pubmed-meshheading:15067095-HLA-B7 Antigen, pubmed-meshheading:15067095-Heat-Shock Proteins, pubmed-meshheading:15067095-Molecular Chaperones, pubmed-meshheading:15067095-Molecular Weight, pubmed-meshheading:15067095-Protein Binding, pubmed-meshheading:15067095-Protein Processing, Post-Translational, pubmed-meshheading:15067095-Protein Subunits, pubmed-meshheading:15067095-Rats, pubmed-meshheading:15067095-Rats, Inbred Lew, pubmed-meshheading:15067095-Spleen, pubmed-meshheading:15067095-Transgenes
pubmed:year
2004
pubmed:articleTitle
HLA-B27 in transgenic rats forms disulfide-linked heavy chain oligomers and multimers that bind to the chaperone BiP.
pubmed:affiliation
Harold C. Simmons Arthritis Research Center and Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't