T cell Recognition of Type II Collagen - A Cartilage Glycoprotein of Importance for Autoimmune Arthritis
(1996)- Abstract
- Collagen-induced arthritis (CIA) is a T cell-dependent autoimmune disease that serves as an animal model for human rheumatoid arthritis. CIA can be induced in H-2q mice by a single immunization with the cartilage-specific protein type II collagen (CII). This study has focused on CII immunity and tolerance with respect to the interactions between antigen, antigen-presenting cells and T cells. CIA-resistant mice (H-2p) became susceptible by transgenic expression of the MHC class II Aqß-chain, despite that the Aqß-chain and Apß-chain differ only by 4 amino acids, thus demonstrating the impact of MHC class II polymorphism on development of autoimmune disease. Furthermore, the T cell response elicited after rat CII-immunization in H-2q mice was... (More)
- Collagen-induced arthritis (CIA) is a T cell-dependent autoimmune disease that serves as an animal model for human rheumatoid arthritis. CIA can be induced in H-2q mice by a single immunization with the cartilage-specific protein type II collagen (CII). This study has focused on CII immunity and tolerance with respect to the interactions between antigen, antigen-presenting cells and T cells. CIA-resistant mice (H-2p) became susceptible by transgenic expression of the MHC class II Aqß-chain, despite that the Aqß-chain and Apß-chain differ only by 4 amino acids, thus demonstrating the impact of MHC class II polymorphism on development of autoimmune disease. Furthermore, the T cell response elicited after rat CII-immunization in H-2q mice was focused towards the 256-270 peptide of rat CII, and did not crossreact with the corresponding mouse peptide, despite only a single amino acid difference (Glu266 in rat CII, Asp266 in mouse CII). Moreover, the variable glycosylation of this determinant elicited a heterogenous T cell response in terms of T cell receptor structure, in which distinct T cells recognized different levels of glycosylation. Unlike conventional soluble antigens, CII was preferentially presented by macrophages and was not presented by dendritic cells. Furthermore, B cells from naive mice but not from CII-immunized mice presented CII, suggesting a tolerogenic role for CII-reactive B cells. Finally, when the CII 256-270 determinant was expressed in the systemically occurring type I collagen, neither a T cell response, B cell response, nor CIA development was observed, demonstrating that the restricted tissue-distribution of the auto-antigen is a critical factor influencing the development of autoimmune arthritis. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/28259
- author
- Michaëlsson, Erik
- supervisor
- opponent
-
- Matzinger, Polly, NIH, Bethesda, MD, USA
- publishing date
- 1996
- type
- Thesis
- publication status
- published
- subject
- keywords
- Skelett, antigen presentation / autoimmunity / glycopeptide / immunology / MHC class II / post-translational modification / T cell receptor / transgene, rheumatology locomotion, muscle system, Skeleton, muskelsystem, reumatologi, Biochemistry, Metabolism, Biokemi, metabolism
- pages
- 62 pages
- publisher
- Center for Molecular Biomedicine, Lund University
- defense location
- Lecture hall A at Kemicentrum, Lund
- defense date
- 1996-04-04 09:15:00
- external identifiers
-
- other:ISRN: LUMEDW/MEIF-1-SE
- ISBN
- 91-628-1921-6
- language
- English
- LU publication?
- no
- additional info
- The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Medical Inflammation Research (013212019)
- id
- 127a5e07-d70a-4ab2-aa4e-d580e9f85437 (old id 28259)
- date added to LUP
- 2016-04-04 10:36:01
- date last changed
- 2018-11-21 20:59:42
@phdthesis{127a5e07-d70a-4ab2-aa4e-d580e9f85437, abstract = {{Collagen-induced arthritis (CIA) is a T cell-dependent autoimmune disease that serves as an animal model for human rheumatoid arthritis. CIA can be induced in H-2q mice by a single immunization with the cartilage-specific protein type II collagen (CII). This study has focused on CII immunity and tolerance with respect to the interactions between antigen, antigen-presenting cells and T cells. CIA-resistant mice (H-2p) became susceptible by transgenic expression of the MHC class II Aqß-chain, despite that the Aqß-chain and Apß-chain differ only by 4 amino acids, thus demonstrating the impact of MHC class II polymorphism on development of autoimmune disease. Furthermore, the T cell response elicited after rat CII-immunization in H-2q mice was focused towards the 256-270 peptide of rat CII, and did not crossreact with the corresponding mouse peptide, despite only a single amino acid difference (Glu266 in rat CII, Asp266 in mouse CII). Moreover, the variable glycosylation of this determinant elicited a heterogenous T cell response in terms of T cell receptor structure, in which distinct T cells recognized different levels of glycosylation. Unlike conventional soluble antigens, CII was preferentially presented by macrophages and was not presented by dendritic cells. Furthermore, B cells from naive mice but not from CII-immunized mice presented CII, suggesting a tolerogenic role for CII-reactive B cells. Finally, when the CII 256-270 determinant was expressed in the systemically occurring type I collagen, neither a T cell response, B cell response, nor CIA development was observed, demonstrating that the restricted tissue-distribution of the auto-antigen is a critical factor influencing the development of autoimmune arthritis.}}, author = {{Michaëlsson, Erik}}, isbn = {{91-628-1921-6}}, keywords = {{Skelett; antigen presentation / autoimmunity / glycopeptide / immunology / MHC class II / post-translational modification / T cell receptor / transgene; rheumatology locomotion; muscle system; Skeleton; muskelsystem; reumatologi; Biochemistry; Metabolism; Biokemi; metabolism}}, language = {{eng}}, publisher = {{Center for Molecular Biomedicine, Lund University}}, title = {{T cell Recognition of Type II Collagen - A Cartilage Glycoprotein of Importance for Autoimmune Arthritis}}, year = {{1996}}, }