T cells in Autoimmunity: studies on murine type II collagen-induced arthritis

Alexandre Corthay

Research output: ThesisDoctoral Thesis (compilation)

Abstract

Collagen-induced arthritis (CIA) is a mouse model for rheumatoid arthritis, in which autoimmunity is induced by immunization with type II collagen (CII), a cartilage-specific protein. In the present work, alpha/beta T cells were shown to be required for CIA and for the production of anti-CII IgG antibodies, whereas gamma/delta T cells were neither necessary nor sufficient for development of CIA. Approximately 8% of total peripheral T cells in normal mice were found to express two distinct T cell receptor (TCR) alpha chains at the surface, revealing a lack of phenotypic allelic exclusion in TCR alpha. However, the presence of such a high numbers of potentially multireactive T cells did not increase susceptibility to CIA. We also investigated the occurance of spontaneous arthritis in male DBA/1 mice, the most frequently used strain for CIA, and revealed that it is an alpha/beta T cell-independent enthesopathy that was histologically very different from CIA.

Finally, we determined the T cell epitopes on CII, and the TCR structures used for their recognition. Posttranslational modifications (hydroxylation and variable glycosylation) of a single lysine at position 264 of CII were shown to generate four distinct T cell determinants that were specifically recognized by distinct T cell subsets with distinct TCR repertoires. Most T cells, after immunization with CII, recognized CII(256-270) glycosylated with a monosaccharide. The observation that the immunodominant T cell determinant in CIA is a glycopeptide, suggests that induction of self-tolerance may be rendered more difficult by posttranslational glycosylations of proteins. Under special circumstances, like trauma, inflammation or aging, creation of new self epitopes by posttranslational modifications may trigger an autoimmune attack.
Original languageEnglish
QualificationDoctor
Awarding Institution
  • Immunology
Supervisors/Advisors
  • [unknown], [unknown], Supervisor, External person
Award date2000 Mar 10
Publisher
Print ISBNs91-628-4037-1
Publication statusPublished - 2000

Bibliographical note

Defence details

Date: 2000-03-10
Time: 13:00
Place: Rune Grubb Salen, BMC, Sölvegatan 19, Lund, Sweden

External reviewer(s)

Name: Kollias, George
Title: Professor
Affiliation: Hellenic Pasteur Institute, Athens, Greece

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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)

Subject classification (UKÄ)

  • Immunology in the medical area

Keywords

  • Immunologi
  • Autoimmunity / T lymphocytes / collagen-induced arthritis / Glycosylation / TCR
  • transplantation
  • serology
  • Immunology
  • serologi
  • Skeleton
  • muscle system
  • rheumatology locomotion
  • Skelett
  • muskelsystem
  • reumatologi

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