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

来源于胶原诱导性关节炎DBA/1小鼠的T细胞克隆(K-102)与溴化氰片段CB11(278个氨基酸)发生反应。我们制备了10个氨基酸相互重叠的20聚体合成肽。根据与K-102细胞的反应性，确定其表位为N-末端60-81肽(N60-81)。由于N60-81不仅与K-102细胞有反应，而且与II型胶原(CII)免疫的DBA/1小鼠的淋巴结淋巴细胞也有反应，所以N60-81不是K-102细胞所特有的，而是被认为是CII免疫的T淋巴细胞T细胞库中关节形成的关键表位。该N60-81本身不具有关节炎原性，用该肽免疫前可通过天然CII致敏来抑制胶原性关节炎(CA)的发展。此外，N60-81免疫的小鼠外周血淋巴细胞与N60-81无反应，提示N60-81诱导对CII的耐受，继而免疫CII导致非关节炎。此外，与CII联合免疫时，定点替代模拟肽IIC60-81(S68，78，80)对CA的诱导有抑制作用。这些结果表明，N60-81和IIC60-81(S68，78，80)可能是多肽疫苗治疗CA的有用多肽，可能为治疗人类RA提供一种有前途的策略。

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.