Snyder Thomas M, Gittelman Rachel M, Klinger Mark, May Damon H, Osborne Edward J, Taniguchi Ruth, Jabran Zahid H, Kaplan Ian M, Dines Jennifer N, Noakes Matthew T, Pandya Ravi, Chen Xiaoyu, Elasady Summer, Svejnoha Emily, Ebert Peter, Pesesky Mitchell W, De Almeida Patricia, O'Donnell Hope, DeGottardi Quinn, Keitany Gladys, Lu Jennifer, Vong Allen, Elyanow Rebecca, Fields Paul, Al-Asadi Hussein, Greissl Julia, Baldo Lance, Semprini Simona, Cerchione Claudio, Nicolini Fabio, Mazza Massimiliano, Delmonte Ottavia M, Dobbs Kerry, Laguna-Goya Rocio, Carreño-Tarragona Gonzalo, Barrio Santiago, Imberti Luisa, Sottini Alessandra, Quiros-Roldan Eugenia, Rossi Camillo, Biondi Andrea, Bettini Laura Rachele, D'Angio Mariella, Bonfanti Paolo, Tompkins Miranda F, Alba Camille, Dalgard Clifton, Sambri Vittorio, Martinelli Giovanni, Goldman Jason D, Heath James R, Su Helen C, Notarangelo Luigi D, Paz-Artal Estela, Martinez-Lopez Joaquin, Howie Bryan, Carlson Jonathan M, Robins Harlan S
Adaptive Biotechnologies, Seattle, WA, United States.
Microsoft Research, Redmond, WA, United States.
Front Immunol. 2025 Jan 7;15:1488860. doi: 10.3389/fimmu.2024.1488860. eCollection 2024.
T cells are involved in the early identification and clearance of viral infections and also support the development of antibodies by B cells. This central role for T cells makes them a desirable target for assessing the immune response to SARS-CoV-2 infection.
Here, we combined two high-throughput immune profiling methods to create a quantitative picture of the T-cell response to SARS-CoV-2. First, at the individual level, we deeply characterized 3 acutely infected and 58 recovered COVID-19 subjects by experimentally mapping their CD8 T-cell response through antigen stimulation to 545 Human Leukocyte Antigen (HLA) class I presented viral peptides. Then, at the population level, we performed T-cell repertoire sequencing on 1,815 samples (from 1,521 COVID-19 subjects) as well as 3,500 controls to identify shared "public" T-cell receptors (TCRs) associated with SARS-CoV-2 infection from both CD8 and CD4 T cells.
Collectively, our data reveal that CD8 T-cell responses are often driven by a few immunodominant, HLA-restricted epitopes. As expected, the T-cell response to SARS-CoV-2 peaks about one to two weeks after infection and is detectable for at least several months after recovery. As an application of these data, we trained a classifier to diagnose SARS-CoV-2 infection based solely on TCR sequencing from blood samples, and observed, at 99.8% specificity, high early sensitivity soon after diagnosis (Day 3-7 = 85.1% [95% CI = 79.9-89.7]; Day 8-14 = 94.8% [90.7-98.4]) as well as lasting sensitivity after recovery (Day 29+/convalescent = 95.4% [92.1-98.3]).
The approaches described in this work provide detailed insights into the adaptive immune response to SARS-CoV-2 infection, and they have potential applications in clinical diagnostics, vaccine development, and monitoring.
T细胞参与病毒感染的早期识别和清除，还支持B细胞产生抗体。T细胞的这一核心作用使其成为评估对SARS-CoV-2感染免疫反应的理想靶点。
在此，我们结合两种高通量免疫分析方法，以创建T细胞对SARS-CoV-2反应的定量图景。首先，在个体水平上，我们通过实验绘制3例急性感染和58例康复的COVID-19患者的CD8 T细胞对545种人类白细胞抗原（HLA）I类呈递的病毒肽的反应，对其进行了深入表征。然后，在群体水平上，我们对1815份样本（来自1521例COVID-19患者）以及3500份对照进行了T细胞受体库测序，以从CD8和CD4 T细胞中识别与SARS-CoV-2感染相关的共享“公共”T细胞受体（TCR）。
总体而言，我们的数据表明，CD8 T细胞反应通常由少数免疫显性、HLA限制的表位驱动。正如预期的那样，T细胞对SARS-CoV-2的反应在感染后约一到两周达到峰值，并且在康复后至少几个月内都可检测到。作为这些数据的应用，我们训练了一个分类器，仅基于血液样本中的TCR测序来诊断SARS-CoV-2感染，并观察到，在特异性为99.8%的情况下，诊断后不久（第3 - 7天 = 85.1% [95% CI = 79.9 - 89.7]；第8 - 14天 = 94.8% [90.7 - 98.4]）具有较高的早期敏感性，以及康复后持久的敏感性（第29天及以后/恢复期 = 95.4% [92.1 - 98.3]）。
本研究中描述的方法为SARS-CoV-2感染的适应性免疫反应提供了详细的见解，并且它们在临床诊断、疫苗开发和监测方面具有潜在应用。
