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


CONCLUSIONS
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.
von Delwig
Alexei
A
Institute of Cellular Medicine, Newcastle University, Framlington Place, Newcastle upon Tyne, NE2 4HH, UK. alexei.delwig@ncl.ac.uk
Altmann
Daniel M
DM
Charlton
Fraser G
FG
McKie
Norman
N
Isaacs
John D
JD
Holmdahl
Rikard
R
Robinson
John H
JH
D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology*; D002455:Cell Division / Q000276:immunology; D002478:Cells, Cultured; D024043:Collagen Type II / Q000276:immunology*; D004306:Dose-Response Relationship, Immunologic; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D006031:Glycosylation; D015234:HLA-A Antigens / Q000276:immunology*; D059811:HLA-DRB1 Chains; D006614:Hindlimb / Q000276:immunology / Q000473:pathology; D006801:Humans; D006825:Hybridomas / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D013601:T-Lymphocytes / Q000276:immunology*
D024043:Collagen Type II; D018984:Epitopes, T-Lymphocyte; D015234:HLA-A Antigens; D059811:HLA-DRB1 Chains; C487961:HLA-DRB1*01:01 antigen