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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
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
external identifiers
  • Other:ISRN: LUMEDW/MEIF-1-SE
ISBN
91-628-1921-6
language
English
LU publication?
no
id
127a5e07-d70a-4ab2-aa4e-d580e9f85437 (old id 28259)
date added to LUP
2007-06-11 10:16:07
date last changed
2016-09-19 08:45:05
@misc{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},
  keyword      = {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},
  pages        = {62},
  publisher    = {ARRAY(0x8cc3f80)},
  title        = {T cell Recognition of Type II Collagen - A Cartilage Glycoprotein of Importance for Autoimmune Arthritis},
  year         = {1996},
}