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

Research output: ThesisDoctoral Thesis (compilation)

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.

Details

Authors
  • Erik Michaëlsson
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Immunology in the medical area

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
Original languageEnglish
QualificationDoctor
Awarding Institution
Supervisors/Assistant supervisor
  • [unknown], [unknown], Supervisor, External person
Award date1996 Apr 4
Publisher
  • Center for Molecular Biomedicine, Lund University
Print ISBNs91-628-1921-6
Publication statusPublished - 1996
Publication categoryResearch
Externally publishedYes

Bibliographic note

Defence details Date: 1996-04-04 Time: 09:15 Place: Lecture hall A at Kemicentrum, Lund External reviewer(s) Name: Matzinger, Polly Title: [unknown] Affiliation: NIH, Bethesda, MD, USA --- 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)

Related research output

A Corthay, Eva Michaëlsson, J Goldschmidt, & Rikard Holmdahl, 1996, (Unpublished) In: Historielärarnas Förenings Årsskrift.

Research output: Contribution to journalArticle

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