T cell responses to a non-glycosylated epitope predominate in type II collagen-immunised HLA-DRB1*0101 transgenic mice
(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:
https://lup.lub.lu.se/record/663720
- author
- von Delwig, Alexei ; Altmann, Daniel M ; Charlton, Fraser G ; McKie, Norman ; Isaacs, John D ; Holmdahl, Rikard LU and Robinson, John H
- organization
- publishing date
- 2007
- 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}}, }