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

von Delwig, Alexei; Altmann, Daniel M; Charlton, Fraser G; McKie, Norman; Isaacs, John D; Holmdahl, Rikard LU and Robinson, John H (2007) In Annals of the Rheumatic Diseases 66(5). p.599-604
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 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 CII259-273 epitope. Results: The incidence of... (More)
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 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 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 nonglycosylated 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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Annals of the Rheumatic Diseases
volume
66
issue
5
pages
599 - 604
publisher
British Medical Association
external identifiers
  • wos:000246018000005
  • scopus:34248151001
ISSN
1468-2060
DOI
10.1136/ard.2006.061945
language
English
LU publication?
yes
id
e5476239-5f9e-49ce-a902-12959bf0bee1 (old id 663720)
date added to LUP
2007-12-19 09:43:21
date last changed
2017-01-01 06:41:59
@article{e5476239-5f9e-49ce-a902-12959bf0bee1,
  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 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 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 nonglycosylated 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.},
  author       = {von Delwig, Alexei and Altmann, Daniel M and Charlton, Fraser G and McKie, Norman and Isaacs, John D and Holmdahl, Rikard and Robinson, John H},
  issn         = {1468-2060},
  language     = {eng},
  number       = {5},
  pages        = {599--604},
  publisher    = {British Medical Association},
  series       = {Annals of the Rheumatic Diseases},
  title        = {T cell responses to a non-glycosylated epitope predominate in type II collagen-immunised HLA-DRB1*0101 transgenic mice},
  url          = {http://dx.doi.org/10.1136/ard.2006.061945},
  volume       = {66},
  year         = {2007},
}