Identification of T cell receptor and its epitope specificty of arthritogenic T cell clone specific to type II collagen : is its epitope limited?

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T cell clone (K-102) derived from DBA/1 mice with collagen-induced arthritis is reactive to cyanogen bromide fragment, CB11 (278 amino acids). We prepared its synthetic peptides of 20 mer in which 10 amino acids are overlapped each other. By the reactivity of K-102 cells with these peptides, its epitope was determined to be N-terminal 60-81peptide (N60-81). Since N60-81 was reactive not only with K-102 cells but also with typeII collagen (CII) -immunized lymphonode lymphocytes of DBA/1 mice, this peptide is not specific to K-102 cells but is considered to be the critical epitope for arthritogenecity (arthritogenic epitope : AE) included in T cell repertoire of CII-immunized T lymphocytes.This N60-81 itself is devoid of arthritogenicity and preimmunization with this peptide suppressed the development of collagen-induced arthritis (CA) by the subsequent sensitization with native CII.In addition, mice immunized with N60-81 showed no reactivity of their peripheral lymphocytes with N60-81 suggesting that N60-81 induced tolerance for CII resulting in nonarthritogenicity by the subsequent immunization with CII.Furthermore, site-directed substituted analogue peptide IIC60-81 (S68,78,80) showed the suppressive effect on the induction of CA when coimmunized with CII.These results indicate that N60-81 and IIC60-81 (S68,78,80) may be useful peptides for peptide vaccinetherapy to treat CA and may provide a promising strategy for the treatment of human RA.