Deciphering and predicting CD4+ T cell immunodominance of influenza virus hemagglutinin.
Deciphering and predicting CD4+ T cell immunodominance of influenza virus hemagglutinin.
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DOI：
10.1084/jem.20200206
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发表时间：
2020-10-05
期刊：
影响因子：
--
通讯作者：
Sallusto F
中科院分区：
文献类型：
--
作者：
Cassotta A;Paparoditis P;Geiger R;Mettu RR;Landry SJ;Donati A;Benevento M;Foglierini M;Lewis DJM;Lanzavecchia A;Sallusto F
我们探索了人类CD4T细胞对H1型流感血凝素免疫优势的本质，并证明了幼稚的谱系非常广泛，而记忆谱系则选择了高可能性被树突状细胞处理和呈递的多肽。鉴于CD4+T辅助细胞(Th)在诱导抗体和细胞毒性T细胞反应中的重要作用，人们很好地认识到它们的重要性。然而，决定复杂蛋白抗原中免疫优势表位选择的机制仍然不清楚。在这里，我们使用体外刺激记忆T细胞和筛选初始和记忆T细胞库，结合T细胞克隆和TCR测序，剖析了人类对抗流感大流行H1血凝素(H1-HA)的初始和记忆CD4+T细胞库。我们发现幼稚的CD4+T细胞有广泛的谱系，能够识别跨越整个H1-HA序列的自然处理的和隐蔽的多肽。相比之下，记忆Th细胞主要针对少数几个免疫优势肽，这些肽很容易被基于MHC-II的质谱学检测到，并通过结构可及性分析进行预测。总而言之，这些发现揭示了大量针对隐蔽H1-HA多肽的幼稚T细胞的存在，并表明抗原处理是决定免疫优势的主要限制因素。
We explored the nature of the human CD4 T cell immunodominance to influenza H1 hemagglutinin and demonstrate that the naïve repertoire is very broad, while the memory repertoire becomes selected toward peptides with a high likelihood to be processed and presented by dendritic cells. The importance of CD4+ T helper (Th) cells is well appreciated in view of their essential role in the elicitation of antibody and cytotoxic T cell responses. However, the mechanisms that determine the selection of immunodominant epitopes within complex protein antigens remain elusive. Here, we used ex vivo stimulation of memory T cells and screening of naive and memory T cell libraries, combined with T cell cloning and TCR sequencing, to dissect the human naive and memory CD4+ T cell repertoire against the influenza pandemic H1 hemagglutinin (H1-HA). We found that naive CD4+ T cells have a broad repertoire, being able to recognize naturally processed as well as cryptic peptides spanning the whole H1-HA sequence. In contrast, memory Th cells were primarily directed against just a few immunodominant peptides that were readily detected by mass spectrometry–based MHC-II peptidomics and predicted by structural accessibility analysis. Collectively, these findings reveal the presence of a broad repertoire of naive T cells specific for cryptic H1-HA peptides and demonstrate that antigen processing represents a major constraint determining immunodominance.
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影响因子：
4.4
作者：
Cox, Juergen;Neuhauser, Nadin;Mann, Matthias
通讯作者：
Mann, Matthias
影响因子：
100.3
作者：
Mohan, James F.;Unanue, Emil R.
通讯作者：
Unanue, Emil R.
影响因子：
7
作者：
Mellins ED;Stern LJ
通讯作者：
Stern LJ
DOI：
10.4049/jimmunol.1102661
发表时间：
2012-05-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Jenkins MK;Moon JJ
通讯作者：
Moon JJ
影响因子：
6.4
作者：
Jensen, Kamilla Kjaergaard;Andreatta, Massimo;Nielsen, Morten
通讯作者：
Nielsen, Morten