Human HLA-A0201-restricted cytotoxic T lymphocyte recognition of influenza A is dominated by T cells bearing the V beta 17 gene segment.
Human HLA-A0201-restricted cytotoxic T lymphocyte recognition of influenza A is dominated by T cells bearing the V beta 17 gene segment.
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DOI：
10.1084/jem.181.1.79
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发表时间：
1995-01-01
期刊：
影响因子：
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通讯作者：
Borysiewicz LK
中科院分区：
文献类型：
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作者：
Lehner PJ;Wang EC;Moss PA;Williams S;Platt K;Friedman SM;Bell JI;Borysiewicz LK
主要的组织相容性复合体i类限制性细胞毒性T淋巴细胞（CTL）反应在人类病毒感染的清除中是重要的。甲型流感感染后，来自基质蛋白M58-66的肽在MHC等位基因HLA-A0201的背景下出现，并在大多数HLA-A0201受试者中检测到由此产生的CTL反应。初步研究表明，m58 -66特异性CTL克隆显示保守的T细胞受体(TCR) α和β基因片段。我们通过测定21名无关HLA-A0201受试者在M58-66特异性CTL系发育过程中V β 17的表达，并分析M58-66特异性CTL克隆对TCR的使用情况，解决了这一观察结果的重要性。TCR V β 17是主要的V β片段，CD8 V β 17扩增与M58-66特异性裂解相关。来自5名受试者的限制性稀释分析显示，M58-66 CTL前体频率在1/54,000和小于1/250,000之间变化，并且高达85%的基质肽（M58-66）特异性CTL使用V β 17基因片段。M58-66特异性CTL反应依赖于先前的病毒暴露和特异性V β 17扩增，因为在脐带血中没有发现，尽管V β 17+ CD8+ T细胞亚群容易扩增。对来自13名受试者的38个m58 -66特异性V β 17转录本的序列分析显示，CDR3区域广泛保守，包括一个精氨酸-丝氨酸基序的保守。为了测试这种CTL反应对V β 17基因片段的依赖性，在产生m58 -66特异性CTL之前，外周血淋巴细胞中CD8+ TCR V β 17+细胞被耗尽。在大多数情况下，这种消耗阻断或严重减少了m58 -66特异性反应的产生，并且在有限的稀释条件下可以消除m58 -66特异性CTL前体。这些研究揭示了这种自然的人类免疫反应依赖于特定的TCR基因片段。
The major histocompatibility complex class I-restricted cytotoxic T lymphocyte (CTL) response is important in the clearance of viral infections in humans. After influenza A infection, a peptide from the matrix protein, M58-66, is presented in the context of the MHC allele HLA-A0201 and the resulting CTL response is detectable in most HLA- A0201 subjects. An initial study suggested that M58-66-specific CTL clones show conserved T cell receptor (TCR) alpha and beta gene segments. We have addressed the significance of this observation by determining the expression of V beta 17 during the development of M58- 66-specific CTL lines in 21 unrelated HLA-A0201 subjects, and analyzing TCR usage by M58-66-specific CTL clones. TCR V beta 17 was the dominant V beta segment used and CD8 V beta 17 expansion correlated with M58-66- specific lysis. Limiting dilution analysis from five subjects showed the M58-66 CTL precursor frequency to vary between 1/54,000 and less than 1/250,000, and that up to 85% of the matrix peptide (M58-66)- specific CTL used the V beta 17 gene segment. The M58-66 specific CTL response was dependent on previous viral exposure and specific V beta 17 expansion, as it was not found in cord blood, despite a readily expandable V beta 17+ CD8+ T cell subpopulation. Sequence analysis of 38 M58-66-specific V beta 17 transcripts from 13 subjects revealed extensive conservation in the CDR3 region including conservation of an arginine-serine motif. To test the dependence of this CTL response on the V beta 17 gene segment, peripheral blood lymphocytes were depleted of CD8+ TCR V beta 17+ cells, before the generation of M58-66-specific CTL. In most cases such depletion blocked or severely reduced the generation of the M58-66-specific response, and under limiting dilution conditions could abolish M58-66-specific CTL precursors. These studies reveal the dependence of this natural human immune response on a particular TCR gene segment.