Our previous work showed that the
proteoglycan aggrecan can induce erosive
polyarthritis and
spondylitis in BALB/c mice, and that the G1 domain of the
proteoglycan aggrecan (G1) is the arthritogenic region. In this study, two
T cell epitopes residing on G1 within residues 70-84 (
peptide G5) and 150-169 (
peptide G9) were identified using synthetic
peptides and
aggrecan-specific T cell lines. Two G1-specific T cell hybridomas exclusively responded to
peptide G5. When the G5-specific T cell line was injected intraperitoneally into BALB/c mice, it induced acute inflammatory
arthritis in joints, but only in those that had been injected with the
epitope recognized by these T cells. Furthermore, we also demonstrate that the
keratan sulfate chain(s) (KS) on G1 possess immunosuppressive properties with respect to T and
B cell epitope recognition. T cell lines that recognize both G1 and
peptide G5 show an increased response to G1 after KS is removed.
Antibodies in hyperimmune sera of mice immunized with G1 show increased
epitope recognition (quantitative and qualitative) after KS removal before immunization. These studies reveal that a T cell line specific to an
epitope on the G1 domain of
aggrecan, also recognizing a corresponding mouse G1
epitope, can induce
arthritis by adoptive transfer and homing to the intraarticular
epitope, thereby implicating T cells in
arthritis development caused by immunity to the G1 domain of
aggrecan. Moreover, the presence of KS on G1 can inhibit
arthritis development by suppressing T and
B cell epitope recognition.