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Epitope glycosylati...
Epitope glycosylation plays a critical role for T cell recognition of type II collagen in collagen-induced arthritis
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Corthay, Alexandre (author)
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- Bäcklund, Johan (author)
- Lund University,Lunds universitet,Immunologi,Forskargrupper vid Lunds universitet,Immunology,Lund University Research Groups
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Broddefalk, Johan (author)
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Michaelsson, Erik (author)
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Goldschmidt, Tom J (author)
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Kihlberg, Jan (author)
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Holmdahl, Richard (author)
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(creator_code:org_t)
- 1998
- 1998
- English.
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In: European Journal of Immunology. - 1521-4141. ; 28:8, s. 2580-2590
- Related links:
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http://dx.doi.org/10...
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Abstract
Subject headings
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- Immunization of mice with type II collagen (CII) leads to collagen-induced arthritis (CIA), a model for rheumatoid arthritis. T cell recognition of CII is believed to be a critical step in CIA development. We have analyzed the T cell determinants on CII and the TCR used for their recognition, using twenty-nine T cell hybridomas derived from C3H.Q and DBA/1 mice immunized with rat CII. All hybridomas were specific for the CII(256-270) segment. However, posttranslational modifications (hydroxylation and variable O-linked glycosylation) of the lysine at position 264 generated five T cell determinants that were specifically recognized by different T cell hybridoma subsets. TCR sequencing indicated that each of the five T cell epitopes selected its own TCR repertoire. The physiological relevance of this observation was shown by in vivo antibody-driven depletion of TCR Valpha2-positive T cells, which resulted in an inhibition of the T cell proliferative response in vitro towards the non-modified CII(256-270), but not towards the glycosylated epitope. Most hybridomas (20/29) specifically recognized CII(256-270) glycosylated with a monosaccharide (beta-D-galactopyranose). We conclude that this glycopeptide is immunodominant in CIA and that posttranslational modifications of CII create new T cell determinants that generate a diverse TCR repertoire.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Immunology in the medical area (hsv//eng)
Keyword
- Autoimmunity
- Glycosylation
- T cell
- Collagen
- TCR
Publication and Content Type
- art (subject category)
- ref (subject category)
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