Cytotoxic T lymphocytes specific for murine type II collagen do not trigger arthritis in B10 mice

To investigate the role of cytotoxic T lymphocytes (CTL) in arthritis, we set out to induce CTL specific for murine type II collagen (mCII) in a mouse model. The primary protein sequence of the murine pro-alpha 1(II) was screened for fragments bearing H-2 Db or Kb binding motifs. Six fragments were identified and the corresponding peptides synthesized. One of these peptides, peptide P201 (amino acid 199-208 in the C-propeptide of the murine pro-alpha 1(II), was found to be a strong binder to H-2 Db. When used to treat RMA-S cells at 26 degrees C, peptide P201 induced a four-fold increase of surface expression of H-2 Db. Administration of the P201-treated RMA-S cells into B10 mice (H-2b) induced strong CTL responses against the immunizing collagen peptide. Despite the high frequencies of mCII-specific CTL precursors in the periphery, however, the immunized mice showed no sign of arthritis up to 16 weeks after immunization. Implications of these data for autoimmunity and arthritis are discussed.