Conserved T cell receptor repertoire in primary and memory CD8 T cell responses to an acute viral infection.
Conserved T cell receptor repertoire in primary and memory CD8 T cell responses to an acute viral infection.
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DOI：
10.1084/jem.188.1.71
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发表时间：
1998-07-06
期刊：
影响因子：
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通讯作者：
Ahmed R
中科院分区：
文献类型：
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作者：
Sourdive DJ;Murali-Krishna K;Altman JD;Zajac AJ;Whitmire JK;Pannetier C;Kourilsky P;Evavold B;Sette A;Ahmed R
病毒感染通常诱导强大的CD8T细胞反应，在抗病毒免疫中发挥关键作用。病毒清除后，绝大多数扩增的CD8T细胞发生凋亡，留下稳定数量的记忆细胞。清除急性病毒感染的CD8T细胞和个体中长期存在的CD8记忆池之间的关系尚不完全清楚。为了解决这个问题，我们使用三种方法在淋巴细胞性脉络膜脑膜炎病毒(LCMV)感染的小鼠模型中检测了病毒特异性CD8T细胞的T细胞受体(TCRT)谱：(A)体内定量β链V片段和互补决定区3(CDR3)长度谱系分析(免疫显微镜)；(B)用含有病毒多肽的MHCI类四聚体鉴定LCMV特异性CD8T细胞并与TCRVβ特异性抗体共染色；以及(C)基于对变异肽的识别进行功能性TCR指纹分析。我们比较了CD8T细胞对急性原发和继发性LCMV感染的反应，以及免疫小鼠中病毒特异性记忆T细胞的反应。我们的分析表明，来自几个Vβ家族的CD8T细胞参与了针对优势细胞毒性T淋巴细胞表位(NP118-126)的抗LCMV反应。然而，这种CTL应答的大部分(∼70%)是由于三个特权T细胞群在巨细胞病毒感染期间系统地扩张。约30%的应答由Vβ10+CD8T细胞组成，β链CDR3长度为9个氨基酸，40%由Vβ8.1+(βCDR3=8个氨基酸)和Vβ8.2+细胞(βCDR3=6个氨基酸)组成。最后，我们证明了初级抗病毒CD8T细胞反应的TCR谱系在结构和功能上与记忆池和次级CD8T细胞效应器相似。这些结果表明，记忆细胞是从初次感染期间激活的CD8T细胞池中随机选择的。
Viral infections often induce potent CD8 T cell responses that play a key role in antiviral immunity. After viral clearance, the vast majority of the expanded CD8 T cells undergo apoptosis, leaving behind a stable number of memory cells. The relationship between the CD8 T cells that clear the acute viral infection and the long-lived CD8 memory pool remaining in the individual is not fully understood. To address this issue, we examined the T cell receptor (TCR) repertoire of virus-specific CD8 T cells in the mouse model of infection with lymphocytic choriomeningitis virus (LCMV) using three approaches: (a) in vivo quantitative TCR β chain V segment and complementarity determining region 3 (CDR3) length repertoire analysis by spectratyping (immunoscope); (b) identification of LCMV-specific CD8 T cells with MHC class I tetramers containing viral peptide and costaining with TCR Vβ–specific antibodies; and (c) functional TCR fingerprinting based on recognition of variant peptides. We compared the repertoire of CD8 T cells responding to acute primary and secondary LCMV infections, together with that of virus-specific memory T cells in immune mice. Our analysis showed that CD8 T cells from several Vβ families participated in the anti-LCMV response directed to the dominant cytotoxic T lymphocyte (CTL) epitope (NP118–126). However, the bulk (∼70%) of this CTL response was due to three privileged T cell populations systematically expanding during LCMV infection. Approximately 30% of the response consisted of Vβ10+ CD8 T cells with a β chain CDR3 length of nine amino acids, and 40% consisted of Vβ8.1+ (β CDR3 = eight amino acids) and Vβ8.2+ cells (β CDR3 = six amino acids). Finally, we showed that the TCR repertoire of the primary antiviral CD8 T cell response was similar both structurally and functionally to that of the memory pool and the secondary CD8 T cell effectors. These results suggest a stochastic selection of memory cells from the pool of CD8 T cells activated during primary infection.