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* Departments of Pediatrics and Medicine, University of Tennessee, and
Research Service, Veterans Affairs Medical Center, Memphis, TN 38163;
Collagen Research Unit, Biocenter Oulu, and Department of Medical Biochemistry and Molecular Biology, University of Oulu, Oulu, Finland; and
FibroGen, San Francisco, CA 94080
To establish the role of posttranslational modification in modulating the immune response to collagen, recombinant human type II collagen (rCII) was produced using a yeast expression system (rCIIpic) and a baculovirus expression system (rCIIbac). The biosynthesis of CII requires extensive posttranslational modification including the hydroxylation of prolyl and lysyl residues and glycosylation of selected hydroxylysyl residues. Amino acid analyses indicated that the rCIIbac was adequately hydroxylated at prolyl residues but underhydroxylated at lysyl residues and underglycosylated compared with tissue-derived CII, whereas rCIIpic was adequately hydroxylated at prolyl residues but unhydroxylated at lysyl residues and had no glycosylation. When DBA/1 mice were immunized with rCII, rCIIpic induced a lower incidence of arthritis than tissue-derived CII, whereas rCIIbac induced an intermediate level of arthritis. The severity of the arthritis was significantly lower in mice immunized with rCIIpic compared with mice immunized with tissue-derived CII, whereas that of rCIIbac was intermediate. These data indicate that the degree of lysine hydroxylation and glycosylation plays a role in the induction of arthritis. The recombinant collagens were then compared with tissue-derived CII when given as i.v. or oral tolerogens to suppress arthritis. Both recombinant collagens were less potent than tissue-derived CII, and this decrease in arthritis was associated with a decrease in Ab response to CII. These data suggest that the degree of glysosylation affects the immune response to CII, so that underglycosylated CII is less effective in the induction of arthritis and in its ability to suppress collagen-induced arthritis.
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