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从刺突蛋白中鉴定出三种恢复期 COVID-19 患者的 T 细胞可能识别的特定潜在表位。

Three Specific Potential Epitopes That Could Be Recognized by T Cells of Convalescent COVID-19 Patients Were Identified From Spike Protein.

机构信息

West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China.

Research and Transformation Center for Poisoning Treatment, Laboratory Science & Precision Prevention and Treatment, West China-PUMC C.C. Chen Institute of Health, Sichuan University, Chengdu, China.

出版信息

Front Immunol. 2022 Jan 28;13:752622. doi: 10.3389/fimmu.2022.752622. eCollection 2022.

Abstract

The current coronavirus disease 2019 (COVID-19) vaccines are used to prevent viral infection by inducing neutralizing antibody in the body, but according to the existing experience of severe acute respiratory syndrome coronavirus (SARS) infection, T-cell immunity could provide a longer durable protection period than antibody. The research on SARS-CoV-2-specific T-cell epitope can provide target antigen for the development and evaluation of COVID-19 vaccines, which is conducive to obtain COVID-19 vaccine that can provide long-term protection. For screening specific T-cell epitopes, a SARS-CoV-2 S protein peptide library with a peptide length of 15 amino acids was synthesized. Through flow cytometry to detect percentage of IFN-γ T cells after mixed COVID-19 convalescent patients' peripheral blood mononuclear cell with peptide library, seven peptides (P77, P14, P24, P38, P48, P74, and P84) that can be recognized by the T cells of COVID-19 convalescent patients were found. After excluding the nonspecific cross-reactions with unexposed population, three SARS-CoV-2-specific T-cell potential epitopes (P38, P48, and P84) were finally screened with the positive reaction rates between 15.4% and 48.0% in COVID-19 convalescent patients. This study also provided the HLA allele information of peptide-positive-response COVID-19 convalescent patients, thus predicting the population coverage of these three potential epitopes. Some HLA alleles showed higher frequency of occurrence in COVID-19 patients than in total Chinese population but no HLA alleles related to the T-cell peptide response and the severity of COVID-19. This research provides three potential T-cell epitopes that are helpful for the design and efficacy evaluation of COVID-19 vaccines. The HLA information provided by this research supplies reference significance for subsequent research such as finding the relation of HLA genotype with disease susceptibility.

摘要

当前的 2019 年冠状病毒病(COVID-19)疫苗用于通过在体内诱导中和抗体来预防病毒感染,但根据严重急性呼吸系统综合征冠状病毒(SARS)感染的现有经验,T 细胞免疫提供的保护期可能比抗体更长。对 SARS-CoV-2 特异性 T 细胞表位的研究可为 COVID-19 疫苗的开发和评估提供靶抗原,有利于获得能提供长期保护的 COVID-19 疫苗。为了筛选特异性 T 细胞表位,合成了一个长度为 15 个氨基酸的 SARS-CoV-2 S 蛋白肽文库。通过流式细胞术检测混合 COVID-19 康复患者外周血单个核细胞与肽文库后 IFN-γ T 细胞的百分比,发现了七种可被 COVID-19 康复患者 T 细胞识别的肽(P77、P14、P24、P38、P48、P74 和 P84)。在排除与未暴露人群的非特异性交叉反应后,最终筛选出三个 SARS-CoV-2 特异性 T 细胞潜在表位(P38、P48 和 P84),在 COVID-19 康复患者中的阳性反应率在 15.4%至 48.0%之间。这项研究还为肽阳性反应 COVID-19 康复患者提供了 HLA 等位基因信息,从而预测了这三个潜在表位的人群覆盖范围。一些 HLA 等位基因在 COVID-19 患者中的出现频率高于中国总人口,但没有与 T 细胞肽反应和 COVID-19 严重程度相关的 HLA 等位基因。这项研究提供了三个潜在的 T 细胞表位,有助于 COVID-19 疫苗的设计和疗效评估。本研究提供的 HLA 信息为后续研究,如寻找 HLA 基因型与疾病易感性的关系,提供了参考意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bf80/8831549/e5df45e76c5b/fimmu-13-752622-g001.jpg

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