系统性红斑狼疮患者外周血T细胞TCRβ链CDR3谱系漂移和序列鉴定

Complementarity-determining region 3 analysis of T cell receptor beta chain variable region in peripheral blood mononuclear cells of patients with systemic lupus erythematosus

目的探讨系统性红斑狼疮(SLE)患者外周血T细胞TCRβ链CDR3谱系漂移,为SLE的免疫应答机制和个性化治疗研究提供基础。方法采用免疫扫描谱型分析技术,分析5例正常献血员的CDR3分布特征及5例SLE患者PBMC中T细胞TCRβ链CDR3的优势利用情况,对克隆性增生T细胞的CDR3区进行序列分析。结果5例正常献血员PBMCTCRBVCDR3谱型均呈高斯分布,5例活动型SLE患者24TCRBVCDR3家族均出现不同的优势表达,对单/寡克隆性增生T细胞β链CDR3区基因进行测序,证实存在不同的CDR3序列。结论SLE活动期外周血T细胞TCRβ链CDR3谱系出现明显漂移,提示CDR3的选择性表达可能与SLE的免疫发病机理有关,特异应答的T细胞TCRCDR3序列的确定,将为SLE的发病机制研究和个性化治疗提供新的方法与手段。

Objective To analyze the drift of the complementarity-determining region 3 （CDR3） of T cell receptor （TCR） beta chain variable region （TCR BV） in peripheral blood mononuclear cells （PBMCs） of patients with systemic lupus erythematosus. Methods Immunoscope spectratyping techniques was used to analyze the distribution of TCRβ chain CDR3 in 5 normal blood donors and the dominant CDR3 in the PBMCs in 5 SLE patients. Sequence analysis of the CDR3 region in monoclonal or oligoclonal T cells was performed. Results The spectratypes of TCR BV gene CDR3 region showed Gaussian distribution in the 5 normal blood donors. The 5 SLE patients, however, displayed anomalous proliferation and oligoclonal expansion of the T cells was observed in different TCR BV families with different CDR3 sequences. Conclusion Noticeable drift of TCRβ chain CDR3 can be seen in active SLE, indicating possible association of selective expression of TCR with immune pathogenesis in SLE. Determination of specific TCR CDR3 sequence provides a new means for studying the pathogenesis and personalized treatment of SLE.