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

来源于胶原诱导关节炎的DBA/1小鼠的T细胞克隆（K-102）对溴化氰片段CB11（278个氨基酸）有反应。我们制备了由10个氨基酸相互重叠组成的20 mer的合成肽。通过K-102细胞对这些肽的反应性，确定其表位为n端60-81肽（N60-81）。由于N60-81不仅能与K-102细胞反应，还能与DBA/1小鼠ii型胶原（CII）免疫的淋巴细胞反应，因此该肽不是K-102细胞所特有的，但被认为是CII免疫的T淋巴细胞库中关节炎发生的关键表位（关节炎发生表位：AE）。N60-81本身不具有关节炎原性，用该肽预先免疫可通过随后的天然CII致敏抑制胶原诱导关节炎（CA）的发展。此外，用N60-81免疫的小鼠的外周淋巴细胞对N60-81没有反应性，这表明N60-81诱导了对CII的耐受性，导致随后的CII免疫无关节炎性。此外，位点定向取代类似肽IIC60-81 （S68,78,80）在与CII共免疫时对CA的诱导有抑制作用。这些结果表明，N60-81和IIC60-81 （S68,78,80）可能是肽疫苗治疗CA的有效肽，并可能为治疗人类RA提供有希望的策略。

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.