PMID- 15603880 OWN - NLM STAT- MEDLINE DCOM- 20050331 LR - 20111117 IS - 0198-8859 (Print) IS - 0198-8859 (Linking) VI - 65 IP - 12 DP - 2004 Dec TI - Discordant expression of HLA class II-associated co-chaperones and HLA-DRB alleles in cultured fibroblast-like synoviocytes. PG - 1516-29 AB - 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. FAU - Spurrell, David R AU - Spurrell DR AD - Faculty of Medicine, Memorial University of Newfoundland, St. John's, Newfoundland and Labrador, Canada. FAU - Oldford, Sharon A AU - Oldford SA FAU - Frost, Toby AU - Frost T FAU - Larsen, Bodil AU - Larsen B FAU - Codner, Dianne AU - Codner D FAU - Edgecombe, Allison AU - Edgecombe A FAU - Drover, Sheila AU - Drover S LA - eng PT - Journal Article PL - United States TA - Hum Immunol JT - Human immunology JID - 8010936 RN - 0 (Antigens, Differentiation, B-Lymphocyte) RN - 0 (HLA-D Antigens) RN - 0 (HLA-DM antigens) RN - 0 (HLA-DO antigens) RN - 0 (HLA-DR Antigens) RN - 0 (Histocompatibility Antigens Class II) RN - 0 (Molecular Chaperones) RN - 0 (Recombinant Proteins) RN - 0 (invariant chain) RN - 82115-62-6 (Interferon-gamma) RN - 9007-49-2 (DNA) SB - IM MH - Alleles MH - Antigen Presentation MH - Antigens, Differentiation, B-Lymphocyte/biosynthesis/genetics MH - Arthritis, Rheumatoid/*genetics/*immunology/pathology MH - Base Sequence MH - Cells, Cultured MH - DNA/genetics MH - Fibroblasts/immunology/pathology MH - Gene Expression MH - HLA-D Antigens/biosynthesis/*genetics MH - HLA-DR Antigens/biosynthesis/genetics MH - Histocompatibility Antigens Class II/biosynthesis/genetics MH - Humans MH - Interferon-gamma/pharmacology MH - Molecular Chaperones/biosynthesis/genetics MH - Recombinant Proteins MH - Reverse Transcriptase Polymerase Chain Reaction MH - Synovial Membrane/*immunology/pathology EDAT- 2004/12/18 09:00 MHDA- 2005/04/01 09:00 CRDT- 2004/12/18 09:00 PHST- 2003/12/18 00:00 [received] PHST- 2004/09/03 00:00 [revised] PHST- 2004/09/09 00:00 [accepted] PHST- 2004/12/18 09:00 [pubmed] PHST- 2005/04/01 09:00 [medline] PHST- 2004/12/18 09:00 [entrez] AID - S0198-8859(04)00625-1 [pii] AID - 10.1016/j.humimm.2004.09.005 [doi] PST - ppublish SO - Hum Immunol. 2004 Dec;65(12):1516-29. doi: 10.1016/j.humimm.2004.09.005.