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科学通报  2012 

38kD抗原特异TCR基因修饰T细胞的抗结核抗原活性研究

DOI: 10.1360/972011-711, PP. 1657-1665

Keywords: 结核分枝杆菌,38,kD,抗原,T,细胞受体,基因修饰

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Abstract:

抗原特异T细胞受体(Tcellreceptor,TCR)基因修饰T细胞已被应用于肿瘤、病毒感染过继免疫治疗研究,取得了鼓舞人心的结果,但在结核上未见报道.本研究利用结核分枝杆菌38kD抗原刺激人CD4+,CD8+T细胞,通过分析刺激前后T细胞TCR互补决定区3(complementaritydeterminingregion3,CDR3)谱型,从CD4+,CD8+T细胞中分别筛选出38kD抗原特异的TCRVα11,Vβ8和Vα3,Vβ8基因家族T细胞,聚合酶链式反应(polymerasechainreaction,PCR)扩增获得其α,β链全长基因并插入逆转录病毒载体,构建重组载体pMX-β8-IRES-α11-GFP(pβ8α11)和pMX-β8-IRES-α3-GFP(pβ8α3),分别转染初始CD4+,CD8+T细胞,检测其体外抗结核抗原活性.结果显示,TCR基因修饰的CD4+,CD8+T细胞均表达外源性TCR,不仅能特异性识别抗原,且介导免疫效应功能,表明结核抗原特异TCR基因修饰的T细胞具有应用于多药耐药结核患者过继细胞免疫治疗的可能.

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