T cell responses to a non-glycosylated epitope predominate in type II collagen-immunised HLA-DRB1*0101 transgenic mice. Issue 5 (17th November 2006)

• Record Type: Journal Article
• Authors: von Delwig, Alexei; Altmann, Daniel M; Charlton, Fraser G; McKie, Norman; Isaacs, John D; Holmdahl, Rikard; Robinson, John H
• Is Part Of: Annals of the rheumatic diseases. Volume 66:Issue 5(2007)
• Page Start: 599
• Page End: 604
• Publication Date: 2006-11-17
• Subjects: APC, antigen presenting cells -- CFA, complete Freund's adjuvant -- CIA, collagen-induced arthritis -- DC, dendritic cells -- FITC, fluorescein isothiocyanate -- HLA, human leucocyte antigen -- IFA, incomplete Freund's adjuvant -- MHC-II, major histocompatibility complex class-II -- PBS, phosphate-buffered saline -- PE, phycoerythrin -- RA, rheumatoid arthritis -- TCR, T cell receptor -- TG, transgenic; Rheumatism -- Periodicals; 616.723005
• DOI: 10.1136/ard.2006.061945
• Languages: English
• ISSNs: 0003-4967

Abstract

Abstract : Aim: To study collagen-induced arthritis in human leucocyte antigen (HLA)-DR1 transgenic mice lacking endogenous major histocompatibility complex class II molecules (MHC-II) and to determine T cell specificity against the arthritogenic CII259–273 epitope of type II collagen either unmodified or post-translationally glycosylated at Lys264 . Methods: Arthritis was induced by immunisation with human type II collagen in complete Freund's adjuvant and measured by footpad swelling, clinical score and histology. T cell responses were assessed by proliferation of spleen and lymph node cells and in antigen presentation assays, using T cell hybridomas specific for the glycosylated and non-glycosylated CII259–273 epitope. Results: The incidence of arthritis was 50% in DR1-transgenic mice lacking endogenous MHC-II molecules. Recall T cell responses in draining lymph nodes and spleen were consistently greater against the non-glycosylated epitope than to the glycosylated CII259–273 . Most of the T cell hybridomas generated from CII-immunised mice recognised the non-glycosylated CII epitope and this form of the epitope was also presented with 100-fold higher efficiency and 1 h faster kinetics by both macrophages and dendritic cells. Conclusion: This study shows that T cell responses to the non-glycosylated epitope of heterologous (human) CII are dominant in HLA-DR1 transgenic mice lacking MHC-II, which could contribute to the pathogenicity of autoimmune arthritis.