Comprehensive analysis of T cell immunodominance and immunoprevalence of SARS-CoV-2 epitopes in COVID-19 cases.

Comprehensive analysis of T cell immunodominance and immunoprevalence of SARS-CoV-2 epitopes in COVID-19 cases.
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COVID-19病例中SARS-CoV-2表位的T细胞免疫优势和免疫阳性率综合分析。

DOI:
10.1016/j.xcrm.2021.100204
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发表时间:
2021-02-16
期刊:
Cell reports. Medicine
影响因子:
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Sette A
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其他
文献类型:
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作者:
Tarke A;Sidney J;Kidd CK;Dan JM;Ramirez SI;Yu ED;Mateus J;da Silva Antunes R;Moore E;Rubiro P;Methot N;Phillips E;Mallal S;Frazier A;Rawlings SA;Greenbaum JA;Peters B;Smith DM;Crotty S;Weiskopf D;Grifoni A;Sette A

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T 细胞参与控制 SARS-CoV-2 感染。为了确定不同 SARS-CoV-2 抗原的免疫优势模式并精确测量病毒特异性 CD4+ 和 CD8+ T 细胞,我们研究了 99 例 2019 年冠状病毒病 (COVID-19) 恢复期病例的表位特异性 T 细胞反应。使用跨越整个基因组的 1,925 个肽来探测 SARS-CoV-2 蛋白质组,确保公正地覆盖人类白细胞抗原 (HLA) 等位基因以实现 II 类反应。对于 HLA I 类,我们研究了 28 个突出的 HLA I 类等位基因的另外 5,600 个预测结合表位,覆盖了广泛的全球范围。我们鉴定了数百个 HLA 限制性 SARS-CoV-2 衍生表位。观察到不同的免疫优势模式,CD4+ T 细胞、CD8+ T 细胞和抗体的免疫优势模式有所不同。 I 类和 II 类表位被组合成表位大库,以促进 SARS-CoV-2 特异性 CD4+ 和 CD8+ T 细胞的识别和定量。 T 细胞反应识别每个供体中至少 30-40 个表位 免疫显性与 HLA 结合相关 CD4+ T 细胞的免疫显性区域与抗体表位具有最小重叠 CD8+ T 细胞反应取决于 HLA I 类等位基因的库 Tarke 等人。显示出广泛的 T 细胞库,表明 T 细胞免疫的病毒逃逸不太可能。 CD4 免疫显性区域与 HLA 结合相关,但与普通感冒冠状病毒的高同源性无关。 CD4 很难识别 RBD。表位池可用于优化 T 细胞反应的检测。
T cells are involved in control of SARS-CoV-2 infection. To establish the patterns of immunodominance of different SARS-CoV-2 antigens and precisely measure virus-specific CD4+ and CD8+ T cells, we study epitope-specific T cell responses of 99 convalescent coronavirus disease 2019 (COVID-19) cases. The SARS-CoV-2 proteome is probed using 1,925 peptides spanning the entire genome, ensuring an unbiased coverage of human leukocyte antigen (HLA) alleles for class II responses. For HLA class I, we study an additional 5,600 predicted binding epitopes for 28 prominent HLA class I alleles, accounting for wide global coverage. We identify several hundred HLA-restricted SARS-CoV-2-derived epitopes. Distinct patterns of immunodominance are observed, which differ for CD4+ T cells, CD8+ T cells, and antibodies. The class I and class II epitopes are combined into epitope megapools to facilitate identification and quantification of SARS-CoV-2-specific CD4+ and CD8+ T cells. T cell responses recognize at least 30–40 epitopes in each donor Immunodominance is correlated with HLA binding Immunodominant regions for CD4+ T cells have minimal overlap with antibody epitopes CD8+ T cell responses depend on the repertoire of HLA class I alleles Tarke et al. show a broad T cell repertoire, suggesting that viral escape of T cell immunity is unlikely. CD4 immunodominant regions correlate with HLA binding and not with high common cold coronavirus homology. RBD is poorly recognized by CD4s. Epitope pools can be used to optimize detection of T cell responses.
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