Efficacy of modified recombinant type II collagen in modulating autoimmune arthritis

Previous studies have shown that an analog peptide of the immunodominant T cell determinant of type II collagen (CII), i.e., CII(256-276)(N(263), D(266)), was able to suppress the immune response to CII and the development of arthritis in DR1-transgenic mice. The present study tested the hypothesis that introduction of the same amino acid substitutions into full-length CII might improve the efficacy of the mutant collagen in achieving suppression of autoimmune arthritis.

Using recombinant technology, full-length CII was modified, while the native conformation was retained. Two point mutations were introduced within the immunodominant T cell determinant to convert the F(263) to N and E(266) to D, using a baculovirus expression system that has previously been utilized in the production of recombinant CII (rCII).

The mutant rCII(N(263), D(266)) was capable of reducing the incidence and severity of arthritis as well as the antibody response to CII when administered to DR1-transgenic mice that display susceptibility to collagen-induced arthritis. More importantly, it was significantly more effective than the synthetic analog peptide, CII(256-276)(N(263), D(266)). Its mechanism of suppression may be explained by the secretion of predominantly Th2 cytokines by the T cells immunized with rCII(N(263), D(266)). Administration of rCII(N(263), D(266)) was ineffective in suppressing arthritis in IL4(-/-) mice, suggesting that the profound suppressive effects of rCII(N(263), D(266)) were mediated through the production of interleukin-4.

These findings describe a promising specific immunotherapy for patients with DR1-mediated autoimmunity to CII.