研究揭示預先存在和誘導的SARS-CoV-2特異性CD8+T細胞特徵
作者:
小柯機器人發布時間:2020/11/16 14:02:06
近日,德國弗萊堡大學Christoph Neumann-Haefelin等研究人員合作揭示了預先存在和誘導的SARS-CoV-2特異性CD8+T細胞特徵。2020年11月12日,《自然—醫學》雜誌在線發表了這項成果。
研究人員定義了一組最佳和主要的SARS-CoV-2特異性CD8+T細胞表位。研究人員還應用肽裝載的I類主要組織相容性複合體(pMHCI)四聚體技術對預先存在和誘導的SARS-CoV-2特異性CD8+T細胞進行了高解析度離體分析。研究人員在SARS-CoV-2感染後患有輕度疾病的個體中進行了橫向研究,並縱向評估了3例SARS-CoV-2感染前後的T細胞,從而觀察到快速誘導、延長的收縮以及異源性和功能性交叉反應和誘導性記憶CD8+T細胞反應的出現。
SARS-CoV-2特異性記憶CD8+T細胞表現出與流感特異性CD8+T細胞相當的功能特性,並且在針對靶向刺突(S)和核蛋白(N)的抗SARS-CoV-2抗體血清陰性的SARS-CoV-2恢復期個體中可檢測到。這些結果將交叉反應和誘導的SARS-CoV-2特異性CD8+T細胞反應定義為輕度SARS-CoV-2感染中免疫保護的潛在重要決定因素。
據悉,新興數據表明,針對不同病毒蛋白的SARS-CoV-2特異性CD8+T細胞在70%的恢復期個體中可檢測到。然而,目前很少有關於SARS-CoV-2感染自然過程中已存在和誘導的SARS-CoV-2特異性CD8+T細胞應答的豐度、表型、功能能力和命運的信息。
附:英文原文
Title: Characterization of pre-existing and induced SARS-CoV-2-specific CD8 + T cells
Author: Isabel Schulien, Janine Kemming, Valerie Oberhardt, Katharina Wild, Lea M. Seidel, Saskia Killmer, Sagar, Franziska Daul, Marilyn Salvat Lago, Annegrit Decker, Hendrik Luxenburger, Benedikt Binder, Dominik Bettinger, Oezlem Sogukpinar, Siegbert Rieg, Marcus Panning, Daniela Huzly, Martin Schwemmle, Georg Kochs, Cornelius F. Waller, Alexandra Nieters, Daniel Duerschmied, Florian Emmerich, Henrik E. Mei, Axel Ronald Schulz, Sian Llewellyn-Lacey, David A. Price, Tobias Boettler, Bertram Bengsch, Robert Thimme, Maike Hofmann, Christoph Neumann-Haefelin
Issue&Volume: 2020-11-12
Abstract: Emerging data indicate that SARS-CoV-2-specific CD8+ T cells targeting different viral proteins are detectable in up to 70% of convalescent individuals1,2,3,4,5. However, very little information is currently available about the abundance, phenotype, functional capacity and fate of pre-existing and induced SARS-CoV-2-specific CD8+ T cell responses during the natural course of SARS-CoV-2 infection. Here, we define a set of optimal and dominant SARS-CoV-2-specific CD8+ T cell epitopes. We also perform a high-resolution ex vivo analysis of pre-existing and induced SARS-CoV-2-specific CD8+ T cells, applying peptide-loaded major histocompatibility complex class I (pMHCI) tetramer technology. We observe rapid induction, prolonged contraction and emergence of heterogeneous and functionally competent cross-reactive and induced memory CD8+ T cell responses in cross-sectionally analyzed individuals with mild disease following SARS-CoV-2 infection and three individuals longitudinally assessed for their T cells pre- and post-SARS-CoV-2 infection. SARS-CoV-2-specific memory CD8+ T cells exhibited functional characteristics comparable to influenza-specific CD8+ T cells and were detectable in SARS-CoV-2 convalescent individuals who were seronegative for anti-SARS-CoV-2 antibodies targeting spike (S) and nucleoprotein (N). These results define cross-reactive and induced SARS-CoV-2-specific CD8+ T cell responses as potentially important determinants of immune protection in mild SARS-CoV-2 infection.
DOI: 10.1038/s41591-020-01143-2
Source: https://www.nature.com/articles/s41591-020-01143-2