CHARACTERIZATION OF A PEPTIDE ANALOG OF A DETERMINANT OF TYPE-II COLLAGEN THAT SUPPRESSES COLLAGEN-INDUCED ARTHRITIS

Immunization of susceptible strains of mice with type II collagen (CII ) elicits an autoimmune arthritis known as collagen-induced arthritis (CIA), One analogue peptide of the immunodominant T cell determinant, A9 (CII245-270 (I-260 --> A, A(261) --> B, F-263 --> N)), was previous ly shown to indued a profound suppression of CIA when coadministered a t the time of immunization with CII, In the present study, A9 peptide was administered i.p., orally, intranasally, or i.v. 2 to 4 wk followi ng CII immunization. We found that arthritis was significantly suppres sed even when A9 was administered after disease was induced. To determ ine the mechanism of action of A9, cytokine responses to A9 and wild-t ype peptide A2 by CII-sensitized spleen cells were compared. An increa se in IL-4 and IL-10, but not in IFN-gamma, was found in A9 culture su pernatants, Additionally, cells obtained from A9-immunized mice produc ed higher amounts of IL-4 and IL-10 when cultured with CII compared wi th cells obtained from mice immunized with A2, which produced predomin antly IFN-gamma, Suppression of arthritis could be transferred to naiv e mice using A9-inmune splenocytes, Lastly, phosphorylation of TCR zet a was not altered in the immunoprecipitates from the lysates of cells exposed to analogue peptides (A9 and A10) together with wild-type A2 i n a T cell line and two I-Ag-restricted, CII-specific T hybridomas. We conclude that analogue peptide A9 is effective in suppressing establi shed CIA by inducing T cells to produce a Th2 cytokine pattern in resp onse to CII.