Richards Katherine A, Changrob Siriruk, Thomas Paul G, Wilson Patrick C, Sant Andrea J
David H. Smith Center for Vaccine Biology and Immunology, University of Rochester Medical Center, Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY 14642, USA.
Drukier Institute for Children's Health, Department of Pediatrics, Weill Cornell Medicine, New York, NY 10065, USA.
iScience. 2024 May 17;27(6):109992. doi: 10.1016/j.isci.2024.109992. eCollection 2024 Jun 21.
The studies reported here focus on the impact of pre-existing CD4 T cell immunity on the first encounter with SARS-CoV-2. They leverage PBMC samples from plasma donors collected after a first SARS-CoV-2 infection, prior to vaccine availability and compared to samples collected prior to the emergence of SARS-CoV-2. Analysis of CD4 T cell specificity across the entire SARS-CoV-2 proteome revealed that the recognition of SARS-CoV-2-derived epitopes by CD4 memory cells prior to the pandemic are enriched for reactivity toward non-structural proteins conserved across endemic CoV strains. However, CD4 T cells after primary infection with SARS-CoV-2 focus on epitopes from structural proteins. We observed little evidence for preferential recall to epitopes conserved between SARS-CoV-2 and seasonal CoV, a finding confirmed through use of selectively curated conserved and SARS-unique peptides. Our data suggest that SARS-CoV-2 CD4 T cells elicited by the first infection are primarily established from the naive CD4 T cell pool.
此处报告的研究聚焦于预先存在的CD4 T细胞免疫对首次接触严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的影响。这些研究利用了在首次感染SARS-CoV-2后、疫苗可用之前从血浆捐献者采集的外周血单核细胞（PBMC）样本，并与在SARS-CoV-2出现之前采集的样本进行比较。对整个SARS-CoV-2蛋白质组的CD4 T细胞特异性分析表明，在大流行之前，CD4记忆细胞对SARS-CoV-2衍生表位的识别富含对地方性冠状病毒株中保守的非结构蛋白的反应性。然而，初次感染SARS-CoV-2后的CD4 T细胞则聚焦于结构蛋白的表位。我们几乎没有观察到对SARS-CoV-2和季节性冠状病毒之间保守表位的优先回忆证据，这一发现通过使用选择性筛选的保守肽段和SARS特异性肽段得到了证实。我们的数据表明，首次感染引发的SARS-CoV-2 CD4 T细胞主要是从初始CD4 T细胞库中建立起来的。
