title: Discordant expression of HLA class II-associated co-chaperones and HLA-DRB alleles in cultured fibroblast-like synoviocytes.
abstract: Human leukocyte antigen (HLA)-DR-positive synovial fibroblasts are frequently observed in rheumatoid arthritis (RA) and may be implicated in the autoimmune reaction because RA is associated with certain HLA-DRB1* alleles. The question of whether components of the class II antigen presentation pathway and specific DRB alleles are efficiently expressed by synovial fibroblasts is germane to this hypothesis. To address this, cultured fibroblast-like synoviocytes (cFLS) were analyzed for constitutive and interferon (IFN)-gamma-induced expression of specific DRB alleles and class II-associated cochaperones. IFN-gamma induction of invariant chain, DM, and DR molecules was observed in all cFLS, but expression of specific DR allotypes was variable. Interestingly, DM-modulated epitopes on RA-associated DR molecules were either absent or delayed, despite strong DM expression and a paucity of major histocompatibility complex/class II-associated invariant chain peptide complexes. Altered expression of specific peptide-dependent epitopes on RA-associated HLA-DR molecules suggests differences in antigen presentation by cFLS, which may have implications for the immunopathogenesis of RA.
authors.affiliation: Faculty of Medicine, Memorial University of Newfoundland, St. John's, Newfoundland and Labrador, Canada.
authors.forename: David R
authors.initials: DR
authors.lastname: Spurrell
authors.forename: Sharon A
authors.initials: SA
authors.lastname: Oldford
authors.forename: Toby
authors.initials: T
authors.lastname: Frost
authors.forename: Bodil
authors.initials: B
authors.lastname: Larsen
authors.forename: Dianne
authors.initials: D
authors.lastname: Codner
authors.forename: Allison
authors.initials: A
authors.lastname: Edgecombe
authors.forename: Sheila
authors.initials: S
authors.lastname: Drover
mesh_terms: D000483:Alleles; D017951:Antigen Presentation; D000944:Antigens, Differentiation, B-Lymphocyte / Q000096:biosynthesis / Q000235:genetics; D001172:Arthritis, Rheumatoid / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D001483:Base Sequence; D002478:Cells, Cultured; D004247:DNA / Q000235:genetics; D005347:Fibroblasts / Q000276:immunology / Q000473:pathology; D015870:Gene Expression; D006681:HLA-D Antigens / Q000096:biosynthesis / Q000235:genetics*; D006684:HLA-DR Antigens / Q000096:biosynthesis / Q000235:genetics; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D018832:Molecular Chaperones / Q000096:biosynthesis / Q000235:genetics; D011994:Recombinant Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013583:Synovial Membrane / Q000276:immunology* / Q000473:pathology
chemical_list: D000944:Antigens, Differentiation, B-Lymphocyte; D006681:HLA-D Antigens; C084245:HLA-DM antigens; C046148:HLA-DO antigens; D006684:HLA-DR Antigens; D000949:Histocompatibility Antigens Class II; D018832:Molecular Chaperones; D011994:Recombinant Proteins; C045084:invariant chain; D007371:Interferon-gamma; D004247:DNA