Weingarten-Gabbay Shira, Klaeger Susan, Sarkizova Siranush, Pearlman Leah R, Chen Da-Yuan, Bauer Matthew R, Taylor Hannah B, Conway Hasahn L, Tomkins-Tinch Christopher H, Finkel Yaara, Nachshon Aharon, Gentili Matteo, Rivera Keith D, Keskin Derin B, Rice Charles M, Clauser Karl R, Hacohen Nir, Carr Steven A, Abelin Jennifer G, Saeed Mohsan, Sabeti Pardis C
bioRxiv. 2020 Oct 26:2020.10.02.324145. doi: 10.1101/2020.10.02.324145.
T cell-mediated immunity may play a critical role in controlling and establishing protective immunity against SARS-CoV-2 infection; yet the repertoire of viral epitopes responsible for T cell response activation remains mostly unknown. Identification of viral peptides presented on class I human leukocyte antigen (HLA-I) can reveal epitopes for recognition by cytotoxic T cells and potential incorporation into vaccines. Here, we report the first HLA-I immunopeptidome of SARS-CoV-2 in two human cell lines at different times post-infection using mass spectrometry. We found HLA-I peptides derived not only from canonical ORFs, but also from internal out-of-frame ORFs in Spike and Nucleoprotein not captured by current vaccines. Proteomics analyses of infected cells revealed that SARS-CoV-2 may interfere with antigen processing and immune signaling pathways. Based on the endogenously processed and presented viral peptides that we identified, we estimate that a pool of 24 peptides would provide one or more peptides for presentation by at least one HLA allele in 99% of the human population. These biological insights and the list of naturally presented SARS-CoV-2 peptides will facilitate data-driven selection of peptides for immune monitoring and vaccine development.
T细胞介导的免疫在控制和建立针对SARS-CoV-2感染的保护性免疫中可能起关键作用；然而，负责激活T细胞反应的病毒表位库大多仍不为人知。鉴定在人类白细胞抗原I类（HLA-I）上呈递的病毒肽可揭示细胞毒性T细胞识别的表位以及可能纳入疫苗的表位。在此，我们使用质谱法报告了在感染后不同时间点两种人类细胞系中SARS-CoV-2的首个HLA-I免疫肽组。我们发现HLA-I肽不仅来源于经典开放阅读框（ORF），还来源于刺突蛋白和核蛋白中当前疫苗未涵盖的内部移码ORF。对感染细胞的蛋白质组学分析表明，SARS-CoV-2可能干扰抗原加工和免疫信号通路。基于我们鉴定出的内源性加工和呈递的病毒肽，我们估计一组24种肽将为99%的人类群体中至少一种HLA等位基因提供一种或多种呈递的肽。这些生物学见解以及天然呈递的SARS-CoV-2肽列表将有助于以数据驱动的方式选择用于免疫监测和疫苗开发的肽。
