成年发病狼疮鼠的T细胞受体Vβ基因测序分析  

Sequence analysis of T cell receptor Vβ genes in aged lupus mice

作　　者：周广宇[1] 藤尾圭志[2] 俞戎[2] 山本一彦[2] 

机构地区：[1]吉林大学中日联谊医院风湿科,长春130033 [2]日本东京大学医学部风湿科

出　　处：《中华风湿病学杂志》2005年第8期458-462,共5页Chinese Journal of Rheumatology

基　　金：国家留学基金资助项目(21822097);日本文部省基金资助项目(平成14年12月)

摘　　要：目的分析MRL/lpr和(NZB×NZW)F1两种狼疮鼠成年发病时,广泛浸润于多脏器的T细胞克隆T细胞受体(TCR)Vβ基因编码的氨基酸基序特点,揭示该T细胞克隆的抗原特异性。方法用反转录聚合酶链反应(RT-PCR)分别扩增不同成年发病狼疮鼠个体的肾脏、大脑中的TCRVβ6基因,对扩增产物进行基因克隆和DNA测序分析;单链构象多态性分析法(SSCP)鉴定广泛浸润的T细胞克隆TCRVβ6基因编码的氨基酸基序。结果两种成年发病狼疮鼠的不同个体之间,广泛浸润于多脏器的T细胞克隆TCRVβ6基因的互补决定区3(CDR3)中出现相同的氨基酸基序。结论不同个体成年发病狼疮鼠的多脏器中广泛浸润的T细胞克隆TCRVβ基因的CDR3中出现相同的氨基酸,表明该克隆针对特定的自身抗原。Objective There were some identical T cell elonotypes expanded and accumulated in different organs in aged diseased （NZB×NZW）F1 and MRL/lpr mice. The amino acid motifs in the third complementarity determining region （CDR3） from the T cell receptor （TCR） Vβ chain was analyzed to demonstrate the antigenic specificity of these identical clones. Methods The TCR Vβ6 gene in kidneys and brains from different individuals of aged diseased lupus mice were amplified by reverse transcriptase polymerase chain reaction （RT-PCR） respectively. The amino acid motifs in CDR3 loops of TCR Vβ6 chain were demonstrated by DNA cloning and DNA sequence analysis. The amino acid motifs from the identical T cell clones accumulated in different organs were identified by single-strand conformation polymorphism （SSCP）. Results Some conserved amino acid motifs such as isoleucine （I） and aspartic acid （D） were observed in CDR3 loops of TCR Vβ6 from these identical T cell clones in different individuals of aged diseased （NZB×NZW）F1 mice. Likewise,I, glycine （G） and D or glutamic acid （E） were also found in MRL/lpr mice. Conclusion These identical T cell clones may recognize restricted T cell epitopes on autoantigens and are involved in specific immune responses in SLE.

关 键 词：红斑狼疮 系统性 小鼠 近交MRL LPR 小鼠 近交NZB 受体 抗原 T细胞 氨基酸序列 T细胞受体VΒ基因 DNA测序分析 发病时 狼疮 

分 类 号：R593.241[医药卫生—内科学]