Selective expansion of cross-reactive CD8(+) memory T cells by viral variants.

Selective expansion of cross-reactive CD8(+) memory T cells by viral variants.
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DOI:
10.1084/jem.190.9.1319
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发表时间:
1999-11-01
期刊:
The Journal of experimental medicine
影响因子:
--
通讯作者:
Schumacher TN
Schumacher TN
中科院分区:
其他
文献类型:
--
作者:
Haanen JB;Wolkers MC;Kruisbeek AM;Schumacher TN

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记忆T细胞在免疫应答中对随机抗原变体的作用尚未解决。在这里,我们表明,通过同时染色与两个四聚体的主要组织相容性复合体(MHC)-肽分子,多克隆CD 8 + T细胞对一系列的天然变异体的流感A核蛋白表位的反应是完全占主导地位的罕见的交叉反应性T细胞,从原来的记忆人口扩大。基于生物化学和功能标准,这些交叉反应性细胞毒性T细胞在体外和体内有效地识别亲本和突变体表位。这些结果提供了直接证据,即在感染期间使用的抗原特异性T细胞的库严重依赖于先前的抗原遭遇,并表明多克隆记忆T细胞群可以提供针对一系列抗原变体的保护。
The role of memory T cells during the immune response against random antigenic variants has not been resolved. Here, we show by simultaneous staining with two tetrameric major histocompatibility complex (MHC)–peptide molecules, that the polyclonal CD8+ T cell response against a series of natural variants of the influenza A nucleoprotein epitope is completely dominated by infrequent cross-reactive T cells that expand from an original memory population. Based on both biochemical and functional criteria, these cross-reactive cytotoxic T cells productively recognize both the parental and the mutant epitope in vitro and in vivo. These results provide direct evidence that the repertoire of antigen-specific T cells used during an infection critically depends on prior antigen encounters, and indicate that polyclonal memory T cell populations can provide protection against a range of antigenic variants.