Epitopes described in "Epitope glycosylation plays a critical role for T cell recognition of type II collagen in collagen-induced arthritis."

Article Authors:A Corthay; J Bäcklund; J Broddefalk; E Michaëlsson; T J Goldschmidt; J Kihlberg; R Holmdahl
Article Title:Epitope glycosylation plays a critical role for T cell recognition of type II collagen in collagen-induced arthritis.
Reference Detail
Reference ID:1007050
Abstract: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.
Affiliations:Department of Cell and Molecular Biology, Lund University, Sweden. Alexandre.Corthay@inflam.lu.se
Reference Type:Literature
PubMed ID:9710235
Journal:Eur J Immunol
Journal Volume:28
Article Pages:2580-90
Journal ISSN:0014-2980
Article Chemical List:Immunodominant Epitopes;Receptors, Antigen, T-Cell, alpha-beta;Collagen;DNA
Article MeSH List:Amino Acid Sequence; Animals; Arthritis(etiology; genetics; immunology ); Arthritis, Rheumatoid(etiology; genetics; immunology ); Base Sequence; Collagen(chemistry; immunology ); DNA(genetics ); Disease Models, Animal; Glycosylation; Hybridomas(immunology ); Immunization; Immunodominant Epitopes(chemistry; metabolism ); Male; Mice; Mice, Inbred C3H; Mice, Inbred DBA; Molecular Sequence Data; Molecular Structure; Rats; Receptors, Antigen, T-Cell, alpha-beta(genetics ); T-Lymphocytes(immunology )
Curation Last Updated:2015-07-30 20:19:56