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T cell Recognition of Type II Collagen - A Cartilage Glycoprotein of Importance for Autoimmune Arthritis

Michaëlsson, Erik (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)
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author
supervisor
opponent
  • Matzinger, Polly, NIH, Bethesda, MD, USA
publishing date
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}},
}