Glycopeptide Specificity of Helper T Cells Obtained in Mouse Models for Rheumatoid Arthritis

Holm, Bente; Bäcklund, Johan; Recio, Miguel A. F.; Holmdahl, Rikard; Kihlberg, Jan

doi:10.1002/1439-7633(20021202)3:12<1209::aid-cbic1209>3.0.co;2-0

Cited by 28 publications

(37 citation statements)

References 55 publications

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“…Not surprisingly, peptide 26 , which carries a fully protected galactosyl moiety, did not induce T‐cell activation (data not shown). Also, in line with a previous report by Holm et al,8e glycopeptide 21 , which has a glucosyl (instead of galactosyl) moiety, failed to stimulate two of the T hybridomas, as well as the A9.2 clone (data not shown). This finding emphasises the requirement for an axial HO‐4 group on the carbohydrate molecule for T cell responses.…”

Section: Resultssupporting

confidence: 91%

Synthesis of Glycopeptides from Type II Collagen‐Incorporating Galactosylated Hydroxylysine Mimetics and Their Use in Studying the Fine Specificity of Arthritogenic T Cells

et al. 2005

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Five analogues of the bovine type II collagen (bCII) immunodominant glycopeptide [beta-D-Gal-(5R)-5-Hyl264]CII(256-270) (1) carrying diverse modifications at the critical hydroxylysine (Hyl) 264 side chain were designed and synthesised, to explore the fine specificity of bCII-reactive T cells involved in the initiation and/or regulation of collagen-induced arthritis (CIA), a mouse model for rheumatoid arthritis (RA). Beta-D-galactosyl-(5R)-5-hydroxy-L-lysine (19) and corresponding mimetics (22-25), conveniently protected for solid-phase synthesis, were all obtained by a divergent route involving enantiopure 5-hydroxylated 6-oxo-1,2-piperidinedicarboxylates as the key intermediates. All three bCII-specific T hybridomas used, as well as a recurrent pathogenic CD4+ T-cell clone isolated from bCII-immunised DBA/1 mice, recognised the galactosylated form 1 of the immunodominant bCII (256-270) epitope. These cells were extremely sensitive to changes at the epsilon-amino group of Hyl264, but differed in their pattern of recognition of analogues with a Hyl264 side chain modified at C-5 (i.e. inversion of stereochemistry, methylation). These data further document the importance of collagen post-translational modifications in autoimmunity and in the CIA model in particular, and provide a new insight into the molecular interaction between glycopeptide 1 and the TCR of pathogenic T cells.

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Section: Resultssupporting

confidence: 91%

Synthesis of Glycopeptides from Type II Collagen‐Incorporating Galactosylated Hydroxylysine Mimetics and Their Use in Studying the Fine Specificity of Arthritogenic T Cells

et al. 2005

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“…This is due to the A q -restricted CII260–270 epitope, which is shared between all three species. Furthermore, in line with the biased response towards the galactosylated CII-peptide,17 22 30 periodate treatment of CII almost abolished the recall response in q/q homozygote mice.…”

Section: Resultsmentioning

confidence: 54%

“…Comparable responses were found for both IL-17 (figure 2A) and IFNγ-producing T cells (see online supplementary figure S3). Furthermore, B6 mice primed with chicken CII mounted a full response to periodate-treated chicken CII, showing that B6-derived T cells are not specific for glycosylated CII epitopes, as is the case in H-2 q mice 17 22 30…”

Section: Resultsmentioning

confidence: 97%

C57BL/6 mice need MHC class II Aq to develop collagen-induced arthritis dependent on autoreactive T cells

Bäcklund

Jansson

et al. 2012

Ann Rheum Dis

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“…The following CII259-273 peptides were used: K264 (unmodified rat CII259-273 with lysine at position 264; GIAGFKGEQGPKGEP) and GalOK264, denoted also as Gal264 (CII259-273 with b-D-galactopyranosyl-5-hydroxy-L-lysine at position 264). The synthesis and purification of these peptides were described previously (31,32). The MOG79-96 peptide (mouse myelin oligodendrocytic glycoprotein; GKVTLRIQNVRFSDEGGY) was produced by Schafer-N (Copenhagen, Denmark).…”

Section: Agsmentioning

confidence: 99%

Mice Producing Less Reactive Oxygen Species Are Relatively Resistant to Collagen Glycopeptide Vaccination against Arthritis

Batsalova

Dzhambazov

Klaczkowska

et al. 2010

The Journal of Immunology

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The bottleneck for the induction of collagen-induced arthritis in mice is the recognition of immunodominant type II collagen (CII) peptide (CII259-273) bound to the MHC class II molecule Aq. We have shown previously that the posttranslationally glycosylated lysine at position 264 in this epitope is of great importance for T cell recognition and tolerance induction to CII as well as for arthritis development. The Ncf1 gene, controlling oxidative burst, has been shown to play an important role for immune tolerance to CII. To investigate the effect of oxidation on the efficiency of immune-specific vaccination with MHC class II/glycosylated–CII peptide complexes, we used Ncf1 mutated mice. We demonstrate that normal reactive oxygen species (ROS) levels contribute to the establishment of tolerance and arthritis protection, because only mice with a functional oxidative burst were completely protected from arthritis after administration of the glycosylated CII259–273 peptide in complex with MHC class II. Transfer of T cells from vaccinated mice with functional Ncf1 protein resulted in strong suppression of clinical signs of arthritis in B10.Q mice, whereas the Ncf1 mutated mice as recipients had a weaker suppressive effect, suggesting that ROS modified the secondary rather than the primary immune response. A milder but still significant effect was also observed in ROS deficient mice. During the primary vaccination response, regulatory T cells, upregulation of negative costimulatory molecules, and increased production of anti-inflammatory versus proinflammatory cytokines in both Ncf1 mutated and wild type B10.Q mice was observed, which could explain the vaccination effect independent of ROS.

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Glycopeptide Specificity of Helper T Cells Obtained in Mouse Models for Rheumatoid Arthritis

Cited by 28 publications

References 55 publications

Synthesis of Glycopeptides from Type II Collagen‐Incorporating Galactosylated Hydroxylysine Mimetics and Their Use in Studying the Fine Specificity of Arthritogenic T Cells

Synthesis of Glycopeptides from Type II Collagen‐Incorporating Galactosylated Hydroxylysine Mimetics and Their Use in Studying the Fine Specificity of Arthritogenic T Cells

C57BL/6 mice need MHC class II Aq to develop collagen-induced arthritis dependent on autoreactive T cells

Mice Producing Less Reactive Oxygen Species Are Relatively Resistant to Collagen Glycopeptide Vaccination against Arthritis

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