Glycosylation of type?II collagen is of major importance for T cell tolerance and pathology in collagen-induced arthritis

Bäcklund, Johan; Treschow, Alexandra; Bockermann, Robert; Holm, Bente; Holm, Lotta; Issazadeh‐Navikas, Shohreh; Kihlberg, Jan; Holmdahl, Rikard

doi:10.1002/1521-4141(200212)32:12<3776::aid-immu3776>3.0.co;2-a

Cited by 79 publications

(62 citation statements)

References 24 publications

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“…This results in smaller CII fragments being picked up by APC and presented by MHC class II. Previous studies from our laboratory showed that CII-specific T cells predominantly recognize glycosylation at position 264 in the CII260-270 epitope and that glycosylated CII is more arthritogenic than non-glycosylated CII is [3,11,13,20]. In addition, adoptive transfer of glycopeptidespecific T cells into CII-immunized DBA/1 mice increases the incidence and severity of arthritis as well as the production of CII-specific antibodies [21].…”

Section: Discussionmentioning

confidence: 84%

The major T cell epitope on type II collagen is glycosylated in normal cartilage but modified by arthritis in both rats and humans

et al. 2005

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Type II collagen (CII) is a target for autoreactive T cells in both rheumatoid arthritis and the murine model collagen-induced arthritis. The determinant core of CII has been identified as CII260-270, and the alteration of this T cell epitope by posttranslational modifications is known to be critical for development of arthritis in mice. Using CIIspecific T cell hybridomas we have now shown that the immunodominant T cell epitope in the normal (healthy) human and rat joint cartilage is O-glycosylated at the critical T cell receptor recognition position 264 with a mono-or di-saccharide attached to a hydroxylysine. In contrast, in the arthritic human and rat joint cartilage there are both glycosylated and non-glycosylated CII forms. Glycosylated CII from normal cartilage could not be recognized by T cells reactive to peptides having only lysine or hydroxylysine at position 264, showing that antigen-presenting cells could not degrade the O-linked carbohydrate. Thus, the variable forms of the glycosylated epitope are determined by the structures present in cartilage, and these vary during the disease course. We conclude that the chondrocyte determines the structures presented to the immune system and that these structures are different in normal versus arthritic states.

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Section: Discussionmentioning

confidence: 84%

The major T cell epitope on type II collagen is glycosylated in normal cartilage but modified by arthritis in both rats and humans

et al. 2005

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“…In two subsequent reports, Holmdahl's group demonstrated that protection from collagen-induced arthritis in animals could be afforded by treatment with galactosylated CII peptide and that this epitope is the immunodominant form in RA patients because of incomplete tolerance [21,22]. These data suggest a specific role for adaptive T cell recognition of glycosylated antigens in arthritis disease progression.…”

Section: Glycosylation and Diseasementioning

confidence: 98%

Coming of age: carbohydrates and immunity

Cobb¹,

Kasper²

2005

Eur J Immunol

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Adaptive immune responses have long been considered the "territory" of antigenic proteins, whereas carbohydrates are characterized as T-cell-independent antigens that are not typically recognized by the complete adaptive machinery. The current modus operandi when searching for dominant epitopes is the use of synthetic peptides designed from the primary structure of interesting target proteins; however, there is growing evidence that sugars can also play a critical role in immune recognition. Findings reported in this issue of the European Journal of Immunology begin to shed light on the differences in protein glycosylation that can occur in association with disorders like rheumatoid arthritis and the effect these changes have on collagen recognition by the immune system. Other recent studies have shown that immunodominant glycopeptide "remnant" epitopes as well as glycosylation changes on self-proteins can generate autoimmunity. Finally, some types of carbohydrates are now known to be processed and presented to T cells by class II MHC. Taken together, these advances illustrate a clear importance for carbohydrate recognition in foreign and self antigens by the adaptive immune system. With the common presence of carbohydrate molecules on eukaryotic, prokaryotic, and viral surfaces, the impact of carbohydrates on adaptive immunity is now indisputable.

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“…It was evident that the carbohydrate contents of collagen isolated from commercial shark cartilage capsules were between 5 and 40 % (Merly and Smith 2013). Backlund et al (2002) opined that glycoprotein content of CII is a key element for the recognition of T cell in collagen-induced arthritis models. Recently, Merly and Smith (2013) studied the effect of oral administration of fetal bovine articular cartilage collagen for the treatment of RA.…”

Section: Glycoprotein/carbohydrate Contentmentioning

confidence: 99%

Purification, characterization and antioxidant properties of low molecular weight collagenous polypeptide (37 kDa) prepared from whale shark cartilage (Rhincodon typus)

et al. 2015

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A low molecular weight type-II collagenous polypeptide (CIIp) from whale shark (WS) cartilage was prepared by thermolysin digestion; and examined for their physico-functional and antioxidant properties. The purified collagen was composed of an identical (α 1 ) 3 chains and was characterized as type-II. After hydrolysis with thermolysin, the α-chain of the WS collagen was degraded into smaller peptides with molecular weight ranging from 70 to 20KDa. CIIp was successfully separated from the hydrolysates with molecular weight of approximately 37 kDa. Amino acid analysis of CII, and CIIp indicated imino acid contents of 155 and 121 amino acid residues per 1000 residues, respectively. Differing Fourier transform infrared (FTIR) spectra of CII and CIIp were observed, which suggested that the hydrolysis process by thermolysin affected the secondary structure and molecular order of collagen, particularly the triple-helical structure. The denaturation temperature of CII (34°C) was higher than that of CIIp. Low content of glycoprotein was observed in CII than CIIp due to removal of some polypeptides by thermolysin digestion. The antioxidant activity against 1,1-diphenyl-2-picrylhydrazyl radicals and the reducing power of CIIp was greater than that of CII. The results proposed that the purified CIIp from WS cartilage with excellent antioxidant activities could be the suitable biomaterial for therapeutic applications.

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Glycosylation of type?II collagen is of major importance for T cell tolerance and pathology in collagen-induced arthritis

Cited by 79 publications

References 24 publications

The major T cell epitope on type II collagen is glycosylated in normal cartilage but modified by arthritis in both rats and humans

The major T cell epitope on type II collagen is glycosylated in normal cartilage but modified by arthritis in both rats and humans

Coming of age: carbohydrates and immunity

Purification, characterization and antioxidant properties of low molecular weight collagenous polypeptide (37 kDa) prepared from whale shark cartilage (Rhincodon typus)

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