Discordant expression of HLA class II-associated co-chaperones and HLA-DRB alleles in cultured fibroblast-like synoviocytes

• Published in: Human immunology Vol. 65; no. 12; pp. 1516 - 1529
• Main Authors: Spurrell, David R., Oldford, Sharon A., Frost, Toby, Larsen, Bodil, Codner, Dianne, Edgecombe, Allison, Drover, Sheila
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.12.2004
• Subjects: Alleles; Antigen Presentation; Antigens, Differentiation, B-Lymphocyte - biosynthesis; Antigens, Differentiation, B-Lymphocyte - genetics; Arthritis, Rheumatoid - genetics; Arthritis, Rheumatoid - immunology; Arthritis, Rheumatoid - pathology; Base Sequence; Cells, Cultured; cultured fibroblast-like synoviocytes; DNA - genetics; Fibroblasts - immunology; Fibroblasts - pathology; Gene Expression; Histocompatibility Antigens Class II - biosynthesis; Histocompatibility Antigens Class II - genetics; HLA class II co-chaperones; HLA-D Antigens - biosynthesis; HLA-D Antigens - genetics; HLA-DR Antigens - biosynthesis; HLA-DR Antigens - genetics; HLA-DRB1 alleles; Humans; Interferon-gamma - pharmacology; Molecular Chaperones - biosynthesis; Molecular Chaperones - genetics; Recombinant Proteins; Reverse Transcriptase Polymerase Chain Reaction; rheumatoid arthritis; shared epitope; Synovial Membrane - immunology; Synovial Membrane - pathology; Ii; shared epitope; cFLS; HLA-DRB1 alleles; cultured fibroblast-like synoviocytes; BCL; rheumatoid arthritis; CLIP; mAb; RA; HLA class II co-chaperones; PA; GAM; OA; SE; APC; RT-PCR
• ISSN: 0198-8859; 1879-1166
• DOI: 10.1016/j.humimm.2004.09.005

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)-γ-induced expression of specific DRB alleles and class II-associated cochaperones. IFN-γ 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.