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Ann Rheum Dis. 2007 May;66(5):599-604. Epub 2006 Nov 17.

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

Author information

1
Institute of Cellular Medicine, Newcastle University, Framlington Place, Newcastle upon Tyne, NE2 4HH, UK. alexei.delwig@ncl.ac.uk

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 CII(259-273) epitope of type II collagen either unmodified or post-translationally glycosylated at Lys(264).

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 CII(259-273) 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 CII(259-273). 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.

PMID:
17114189
PMCID:
PMC1954639
DOI:
10.1136/ard.2006.061945
[Indexed for MEDLINE]
Free PMC Article
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