Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

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)
Please use this url to cite or link to this publication:
author
; ; ; ; ; and
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
BMJ Publishing Group
external identifiers
  • wos:000246018000005
  • scopus:34248151001
ISSN
1468-2060
DOI
10.1136/ard.2006.061945
language
English
LU publication?
yes
additional info
The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Department of Experimental Medical Science (013210000), Medical Inflammation Research (013212019)
id
e5476239-5f9e-49ce-a902-12959bf0bee1 (old id 663720)
date added to LUP
2016-04-01 15:33:23
date last changed
2022-01-28 05:54:35
@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    = {{BMJ Publishing Group}},
  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}},
  doi          = {{10.1136/ard.2006.061945}},
  volume       = {{66}},
  year         = {{2007}},
}