SARS-CoV-2 T-cell epitopes define heterologous and COVID-19-induced T-cell recognition
SARS-CoV-2 T-cell epitopes define heterologous and COVID-19-induced T-cell recognition
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SARS-CoV-2 T 细胞表位定义异源和 COVID-19 诱导的 T 细胞识别
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发表时间：
2020
期刊：
影响因子：
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通讯作者：
J. Walz
中科院分区：
文献类型：
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作者：
A. Nelde;Tatjana Bilich;J. Heitmann;Y. Maringer;H. Salih;Malte Roerden;Maren Lübke;Jens Bauer;J. Rieth;Marcel Wacker;Andreas Peter;Sebastian Hörber;B. Traenkle;P. Kaiser;U. Rothbauer;M. Becker;D. Junker;G. Krause;M. Strengert;N. Schneiderhan;M. Templin;T. Joos;D. Kowalewski;Vlatka Stos;M. Fehr;M. Graf;Lena;David Rachfalski;B. Preuß;Ilona Hagelstein;Melanie Märklin;T. Bakchoul;C. Gouttefangeas;O. Kohlbacher;R. Klein;S. Stevanović;H. Rammensee;J. Walz
SARS-CoV-2 大流行需要快速开发诊断、预防和治疗方法。 CD4+ 和 CD8+ T 细胞介导的免疫对于控制和预防病毒感染至关重要[1-3]。表征 T 细胞免疫的先决条件，也是开发疫苗和免疫疗法的先决条件，是鉴定人类白细胞抗原 (HLA) 上呈递的确切病毒 T 细胞表位[2-8]。这是第一项识别和表征 SARS-CoV-2 康复者 (n = 180) 以及未暴露个体 (n = 185) 中 SARS-CoV-2 特异性和交叉反应 HLA I 类和 HLA-DR T 细胞表位的工作，并确认它们与免疫和 COVID-19 病程的相关性。 SARS-CoV-2 特异性 T 细胞表位能够检测感染后 T 细胞免疫，即使是在血清阴性的康复者中。交叉反应的 SARS-CoV-2 T 细胞表位揭示了 81% 的未暴露个体中预先存在的 T 细胞反应，并且验证与普通感冒人类冠状病毒的相似性为 SARS-CoV-2 感染中假定的异源免疫[9]提供了功能基础[10,11]。与未暴露的个体相比，恢复期供体的 T 细胞反应强度和 T 细胞表位识别率显着更高，这表明 SARS-CoV-2 T 细胞反应在主动感染时不仅会发生扩展，而且会发生多样性传播。尽管抗 SARS-CoV-2 抗体水平与 SARS-CoV-2 供体的症状严重程度相关，但 T 细胞反应的强度不会对 COVID-19 的严重程度产生负面影响。相反，在出现轻微的 COVID-19 症状时，SARS-CoV-2 T 细胞反应的多样性会增加，这提供了证据表明免疫的发展需要识别多个 SARS-CoV-2 表位。总之，这项工作中确定的特异性和交叉反应性 SARS-CoV-2 T 细胞表位能够识别异源和感染后 T 细胞免疫，并促进针对 COVID-19 的诊断、预防和治疗措施的开发。
The SARS-CoV-2 pandemic calls for the rapid development of diagnostic, preventive, and therapeutic approaches. CD4+ and CD8+ T cell-mediated immunity is central for control of and protection from viral infections[1-3]. A prerequisite to characterize T-cell immunity, but also for the development of vaccines and immunotherapies, is the identification of the exact viral T-cell epitopes presented on human leukocyte antigens (HLA)[2-8]. This is the first work identifying and characterizing SARS-CoV-2-specific and cross-reactive HLA class I and HLA-DR T-cell epitopes in SARS-CoV-2 convalescents (n = 180) as well as unexposed individuals (n = 185) and confirming their relevance for immunity and COVID-19 disease course. SARS-CoV-2-specific T-cell epitopes enabled detection of post-infectious T-cell immunity, even in seronegative convalescents. Cross-reactive SARS-CoV-2 T-cell epitopes revealed preexisting T-cell responses in 81% of unexposed individuals, and validation of similarity to common cold human coronaviruses provided a functional basis for postulated heterologous immunity[9] in SARS-CoV-2 infection[10,11]. Intensity of T-cell responses and recognition rate of T-cell epitopes was significantly higher in the convalescent donors compared to unexposed individuals, suggesting that not only expansion, but also diversity spread of SARS-CoV-2 T-cell responses occur upon active infection. Whereas anti-SARS-CoV-2 antibody levels were associated with severity of symptoms in our SARS-CoV-2 donors, intensity of T-cell responses did not negatively affect COVID-19 severity. Rather, diversity of SARS-CoV-2 T-cell responses was increased in case of mild symptoms of COVID-19, providing evidence that development of immunity requires recognition of multiple SARS-CoV-2 epitopes. Together, the specific and cross-reactive SARS-CoV-2 T-cell epitopes identified in this work enable the identification of heterologous and post-infectious T-cell immunity and facilitate the development of diagnostic, preventive, and therapeutic measures for COVID-19.