Epitope-Specific Vaccination Limits Clonal Expansion of Heterologous Naive T Cells during Viral Challenge
Epitope-Specific Vaccination Limits Clonal Expansion of Heterologous Naive T Cells during Viral Challenge
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DOI：
10.1016/j.celrep.2016.09.019
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发表时间：
2016-10-11
期刊：
影响因子：
8.8
通讯作者：
Sun, Joseph C.
中科院分区：
文献类型：
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作者：
Johnson, Lexus R.;Orr-El Weizman;Sun, Joseph C.
尽管接种疫苗启动了强大的二次T细胞扩增，但对异型抗原的初级免疫反应的影响仍不明确。在这里，我们表明，由先前感染重组病原体启动的表位特异性记忆CD8(+)T细胞的二次扩增限制了对新的异种抗原具有特异性的初始CD8(+)T细胞的初次扩增，从而抑制了对后续病原体攻击的保护性免疫。幼稚T细胞的抑制程度与回忆反应的大小直接相关。被抑制的初级T细胞启动反应了对抗原可及性的竞争，因为如果初级和次级表位在不同的树突状细胞上表达，克隆扩增不会被抑制。有趣的是，强大的回忆反应并没有影响抗原特异性的NK细胞，这表明适应性和先天淋巴细胞反应具有不同的激活要求，或者发生在不同的解剖位置。这些发现对依赖于靶向多个T细胞表位的病原体疫苗策略具有重要意义。
Despite robust secondary T cell expansion primed by vaccination, the impact on primary immune responses to heterotypic antigens remains undefined. Here we show that secondary expansion of epitope-specific memory CD8(+) T cells primed by prior infection with recombinant pathogens limits the primary expansion of naive CD8(+) T cells with specificity to new heterologous antigens, dampening protective immunity against subsequent pathogen challenge. The degree of naive T cell repression directly paralleled the magnitude of the recall response. Suppressed primary T cell priming reflects competition for antigen accessibility, since clonal expansion was not inhibited if the primary and secondary epitopes were expressed on different dendritic cells. Interestingly, robust recall responses did not impact antigen-specific NK cells, suggesting that adaptive and innate lymphocyte responses possess different activation requirements or occur in distinct anatomical locations. These findings have important implications in pathogen vaccination strategies that depend on the targeting of multiple T cell epitopes.