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

II 型胶原特异性致关节炎 T 细胞克隆的 T 细胞受体及其表位特异性的鉴定：其表位是否有限？

基本信息

批准号：
05670305
负责人：
KAKIMOTO Kiichi
金额：
$ 1.41万
依托单位：
University of Occupational and Environmental Health (1994)Kumamoto University (1993)
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1993
资助国家：
日本
起止时间：
1993 至 1994
项目状态：
已结题

项目摘要

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.

来源于胶原诱导性关节炎DBA/1小鼠的T细胞克隆（K-102）对溴化氰片段CB 11（278个氨基酸）具有反应性。我们制备了20聚体的合成肽，其中10个氨基酸相互重叠。通过K-102细胞与这些肽的反应性，确定其表位为N端60- 81肽（N60-81）。由于N60-81不仅与K-102细胞反应，而且与DBA/1小鼠的II型胶原（CII）免疫的淋巴结淋巴细胞反应，因此该肽对K-102细胞不是特异性的，但被认为是关节炎发生的关键表位（致关节炎表位：这种N60-81本身没有致关节炎性，并且用这种肽预免疫抑制了胶原蛋白的形成。此外，用N60-81免疫的小鼠显示它们的外周淋巴细胞与N60 - 81没有反应性，这表明N60 - 81诱导了对CII的耐受，从而通过随后用CII免疫而导致非致关节炎性。结果表明，N60-81和IIC 60 -81（S68，78，80）与CII共免疫对CA的诱导有抑制作用。