Centre for Cellular and Molecular Physiology, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7BN, UK.
Nuffield Department of Clinical Medicine, University of Oxford, Oxford OX37FZ, UK.
Cell Rep. 2021 May 25;35(8):109179. doi: 10.1016/j.celrep.2021.109179. Epub 2021 May 13.
Understanding and eliciting protective immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an urgent priority. To facilitate these objectives, we profile the repertoire of human leukocyte antigen class II (HLA-II)-bound peptides presented by HLA-DR diverse monocyte-derived dendritic cells pulsed with SARS-CoV-2 spike (S) protein. We identify 209 unique HLA-II-bound peptide sequences, many forming nested sets, which map to sites throughout S including glycosylated regions. Comparison of the glycosylation profile of the S protein to that of the HLA-II-bound S peptides reveals substantial trimming of glycan residues on the latter, likely induced during antigen processing. Our data also highlight the receptor-binding motif in S1 as a HLA-DR-binding peptide-rich region and identify S2-derived peptides with potential for targeting by cross-protective vaccine-elicited responses. Results from this study will aid analysis of CD4 T cell responses in infected individuals and vaccine recipients and have application in next-generation vaccine design.
了解和引发针对严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）的保护性免疫反应是当务之急。为了促进这些目标的实现，我们对与 HLA-DR 多样化单核细胞衍生树突状细胞呈递的 SARS-CoV-2 刺突（S）蛋白脉冲结合的人类白细胞抗原 II 类（HLA-II）结合肽的库进行了分析。我们确定了 209 个独特的 HLA-II 结合肽序列，其中许多形成嵌套集，这些序列映射到 S 中的各个部位，包括糖基化区域。S 蛋白的糖基化谱与 HLA-II 结合的 S 肽的糖基化谱进行比较，发现后者的糖基化残基大量减少，这可能是在抗原加工过程中诱导的。我们的数据还突出了 S1 中的受体结合基序作为 HLA-DR 结合肽丰富的区域，并确定了 S2 衍生的肽具有被交叉保护性疫苗诱导的反应靶向的潜力。这项研究的结果将有助于分析感染个体和疫苗接种者的 CD4 T 细胞反应，并可应用于下一代疫苗设计。
