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T cell responses to a non-glycosylated epitope predominate in type II collagen-immunised HLA-DRB1*0101 transgenic mice

Lookup NU author(s): Dr Alexei von Delwig, Dr Fraser Charlton, Professor John IsaacsORCiD, Professor John Robinson

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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.

Publication metadata

Author(s): Von Delwig A, Altmann DM, Charlton FG, McKie N, Isaacs JD, Holmdahl R, Robinson JH

Publication type: Article

Publication status: Published

Journal: Annals of the Rheumatic Diseases

Year: 2007

Volume: 66

Issue: 5

Pages: 599-604

Print publication date: 01/05/2007

Date deposited: 04/06/2010

ISSN (print): 0003-4967

ISSN (electronic): 1468-2060

Publisher: BMJ Group

URL: http://dx.doi.org/10.1136/ard.2006.061945

DOI: 10.1136/ard.2006.061945

PubMed id: 17114189

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