• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

免疫球蛋白胚系基因多态性影响 SARS-CoV-2 中和抗体的功能。

Immunoglobulin germline gene polymorphisms influence the function of SARS-CoV-2 neutralizing antibodies.

机构信息

Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, 171 77 Stockholm, Sweden.

Department of Cell and Molecular Biology, Karolinska Institutet, 171 77 Stockholm, Sweden.

出版信息

Immunity. 2023 Jan 10;56(1):193-206.e7. doi: 10.1016/j.immuni.2022.12.005. Epub 2022 Dec 12.

DOI:10.1016/j.immuni.2022.12.005
PMID:36574772
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9742198/
Abstract

The human immunoglobulin heavy-chain (IGH) locus is exceptionally polymorphic, with high levels of allelic and structural variation. Thus, germline IGH genotypes are personal, which may influence responses to infection and vaccination. For an improved understanding of inter-individual differences in antibody responses, we isolated SARS-CoV-2 spike-specific monoclonal antibodies from convalescent health care workers, focusing on the IGHV1-69 gene, which has the highest level of allelic variation of all IGHV genes. The IGHV1-6920-using CAB-I47 antibody and two similar antibodies isolated from an independent donor were critically dependent on allele usage. Neutralization was retained when reverting the V region to the germline IGHV1-6920 allele but lost when reverting to other IGHV1-69 alleles. Structural data confirmed that two germline-encoded polymorphisms, R50 and F55, in the IGHV1-69 gene were required for high-affinity receptor-binding domain interaction. These results demonstrate that polymorphisms in IGH genes can influence the function of SARS-CoV-2 neutralizing antibodies.

摘要

人类免疫球蛋白重链（IGH）基因座具有极高的等位基因和结构变异性，因此具有高度的多态性。因此，种系IGH 基因型是个体特有的，这可能会影响对感染和疫苗接种的反应。为了更好地理解抗体反应的个体间差异，我们从康复的医护人员中分离出针对 SARS-CoV-2 刺突蛋白的单克隆抗体，重点关注IGHV1-69 基因，该基因是所有IGHV 基因中具有最高等位基因变异性的基因。使用IGHV1-6920 的 CAB-I47 抗体和从另一个独立供体中分离出的两种类似抗体严重依赖于等位基因的使用。将 V 区回复到种系IGHV1-6920 等位基因时，中和作用得以保留，但回复到其他 IGHV1-69 等位基因时则丧失。结构数据证实，IGHV1-69 基因中的两个种系编码的多态性 R50 和 F55 对于高亲和力受体结合域相互作用是必需的。这些结果表明，IGH 基因中的多态性会影响 SARS-CoV-2 中和抗体的功能。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c68c/9742198/0b2da0333768/gr6_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c68c/9742198/60a403794d92/fx1_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c68c/9742198/e6d418443d11/gr1_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c68c/9742198/bb13205048fe/gr2_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c68c/9742198/bbbe46f7e9eb/gr3_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c68c/9742198/f91a3b4d4632/gr4_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c68c/9742198/add0419632a0/gr5_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c68c/9742198/0b2da0333768/gr6_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c68c/9742198/60a403794d92/fx1_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c68c/9742198/e6d418443d11/gr1_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c68c/9742198/bb13205048fe/gr2_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c68c/9742198/bbbe46f7e9eb/gr3_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c68c/9742198/f91a3b4d4632/gr4_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c68c/9742198/add0419632a0/gr5_lrg.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c68c/9742198/0b2da0333768/gr6_lrg.jpg

相似文献

1
Immunoglobulin germline gene polymorphisms influence the function of SARS-CoV-2 neutralizing antibodies.免疫球蛋白胚系基因多态性影响 SARS-CoV-2 中和抗体的功能。
Immunity. 2023 Jan 10;56(1):193-206.e7. doi: 10.1016/j.immuni.2022.12.005. Epub 2022 Dec 12.
2
Frequent use of IGHV3-30-3 in SARS-CoV-2 neutralizing antibody responses.IGHV3-30-3在严重急性呼吸综合征冠状病毒2中和抗体反应中的频繁使用。
Front Virol. 2023 Mar 1;3:1128253. doi: 10.3389/fviro.2023.1128253.
3
IGHV1-69 polymorphism modulates anti-influenza antibody repertoires, correlates with IGHV utilization shifts and varies by ethnicity.IGHV1-69基因多态性调节抗流感抗体库，与IGHV基因使用的变化相关，且因种族而异。
Sci Rep. 2016 Feb 16;6:20842. doi: 10.1038/srep20842.
4
IgV somatic mutation of human anti-SARS-CoV-2 monoclonal antibodies governs neutralization and breadth of reactivity.人类抗 SARS-CoV-2 单克隆抗体的 IgV 体细胞突变决定了中和作用和反应广度。
JCI Insight. 2021 May 10;6(9):147386. doi: 10.1172/jci.insight.147386.
5
Analysis of B Cell Receptor Repertoires Reveals Key Signatures of the Systemic B Cell Response after SARS-CoV-2 Infection.分析 B 细胞受体文库揭示了 SARS-CoV-2 感染后系统性 B 细胞反应的关键特征。
J Virol. 2022 Feb 23;96(4):e0160021. doi: 10.1128/JVI.01600-21. Epub 2021 Dec 8.
6
Stereotypic neutralizing V antibodies against SARS-CoV-2 spike protein receptor binding domain in patients with COVID-19 and healthy individuals.COVID-19 患者和健康个体中针对 SARS-CoV-2 刺突蛋白受体结合域的刻板中和 V 抗体。
Sci Transl Med. 2021 Jan 27;13(578). doi: 10.1126/scitranslmed.abd6990. Epub 2021 Jan 4.
7
Shared IGHV1-69-encoded neutralizing antibodies contribute to the emergence of L452R substitution in SARS-CoV-2 variants.共享的 IGHV1-69 编码中和抗体有助于 SARS-CoV-2 变体中 L452R 取代的出现。
Emerg Microbes Infect. 2022 Dec;11(1):2749-2761. doi: 10.1080/22221751.2022.2140611.
8
Vaccination of SARS-CoV-2-infected individuals expands a broad range of clonally diverse affinity-matured B cell lineages.SARS-CoV-2 感染个体的疫苗接种会扩增广泛的、克隆多样化的亲和力成熟的 B 细胞谱系。
Nat Commun. 2023 Apr 19;14(1):2249. doi: 10.1038/s41467-023-37972-1.
9
Structure of a Vaccine-Induced, Germline-Encoded Human Antibody Defines a Neutralizing Epitope on the SARS-CoV-2 Spike N-Terminal Domain.疫苗诱导的、种系编码的人抗体结构定义了 SARS-CoV-2 刺突 N 端结构域上的一个中和表位。
mBio. 2022 Jun 28;13(3):e0358021. doi: 10.1128/mbio.03580-21. Epub 2022 Apr 25.
10
Structural Basis of a Human Neutralizing Antibody Specific to the SARS-CoV-2 Spike Protein Receptor-Binding Domain.人类针对 SARS-CoV-2 刺突蛋白受体结合域的中和抗体的结构基础。
Microbiol Spectr. 2021 Oct 31;9(2):e0135221. doi: 10.1128/Spectrum.01352-21. Epub 2021 Oct 13.

引用本文的文献

1
Germline polymorphisms in the immunoglobulin kappa and lambda loci explain variation in the expressed light chain antibody repertoire.免疫球蛋白κ和λ基因座中的种系多态性解释了表达的轻链抗体库的变异。
Res Sq. 2025 Jul 16:rs.3.rs-6994086. doi: 10.21203/rs.3.rs-6994086/v1.
2
Decoding the etiology of immune-mediated inflammatory diseases statistically.从统计学角度解读免疫介导的炎症性疾病的病因。
Front Immunol. 2025 Jun 17;16:1610662. doi: 10.3389/fimmu.2025.1610662. eCollection 2025.
3
Germline polymorphism in the immunoglobulin kappa and lambda loci explain variation in the expressed light chain antibody repertoire.

本文引用的文献

1
Structural basis of broad SARS-CoV-2 cross-neutralization by affinity-matured public antibodies.广谱 SARS-CoV-2 中和抗体亲和力成熟的结构基础。
Cell Rep Med. 2024 Jun 18;5(6):101577. doi: 10.1016/j.xcrm.2024.101577. Epub 2024 May 17.
2
Allelic polymorphism controls autoreactivity and vaccine elicitation of human broadly neutralizing antibodies against influenza virus.等位基因多态性控制着人类广谱中和抗体针对流感病毒的自身反应性和疫苗诱导。
Immunity. 2022 Sep 13;55(9):1693-1709.e8. doi: 10.1016/j.immuni.2022.07.006. Epub 2022 Aug 10.
3
A public antibody class recognizes an S2 epitope exposed on open conformations of SARS-CoV-2 spike.
免疫球蛋白κ和λ基因座中的种系多态性解释了表达的轻链抗体库的变异。
bioRxiv. 2025 Jun 1:2025.05.28.656470. doi: 10.1101/2025.05.28.656470.
4
Vaccination of nonhuman primates elicits a broadly neutralizing antibody lineage targeting a quaternary epitope on the HIV-1 Env trimer.对非人类灵长类动物进行疫苗接种可引发一种广泛中和抗体谱系，该谱系靶向HIV-1包膜三聚体上的一个四级表位。
Immunity. 2025 Jun 10;58(6):1598-1613.e8. doi: 10.1016/j.immuni.2025.04.010. Epub 2025 May 7.
5
Scifer: An R/Bioconductor package for large-scale integration of Sanger sequencing and flow cytometry data of index-sorted single cells.Scifer：一个用于对索引排序的单细胞的桑格测序和流式细胞术数据进行大规模整合的R/Bioconductor软件包。
Immunoinformatics (Amst). 2024 Dec;16:100046. doi: 10.1016/j.immuno.2024.100046. Epub 2024 Oct 29.
6
An allelic atlas of immunoglobulin heavy chain variable regions reveals antibody binding epitope preference resilient to SARS-CoV-2 mutation escape.免疫球蛋白重链可变区的等位基因图谱揭示了抗体结合表位偏好对SARS-CoV-2突变逃逸具有抗性。
Front Immunol. 2025 Jan 7;15:1471396. doi: 10.3389/fimmu.2024.1471396. eCollection 2024.
7
An unbiased comparison of immunoglobulin sequence aligners.免疫球蛋白序列比对工具的无偏比较。
Brief Bioinform. 2024 Sep 23;25(6). doi: 10.1093/bib/bbae556.
8
Ultrasensitive allele inference from immune repertoire sequencing data with MiXCR.使用MiXCR从免疫组库测序数据中进行超灵敏等位基因推断。
Genome Res. 2024 Dec 23;34(12):2293-2303. doi: 10.1101/gr.278775.123.
9
The peculiar features, diversity and impact of citrulline-reactive autoantibodies.瓜氨酸反应性自身抗体的特征、多样性和影响。
Nat Rev Rheumatol. 2024 Jul;20(7):399-416. doi: 10.1038/s41584-024-01124-6. Epub 2024 Jun 10.
10
Structural basis of broad SARS-CoV-2 cross-neutralization by affinity-matured public antibodies.广谱 SARS-CoV-2 中和抗体亲和力成熟的结构基础。
Cell Rep Med. 2024 Jun 18;5(6):101577. doi: 10.1016/j.xcrm.2024.101577. Epub 2024 May 17.
一种公共抗体类别识别 SARS-CoV-2 刺突蛋白开放构象上暴露的 S2 表位。
Nat Commun. 2022 Aug 4;13(1):4539. doi: 10.1038/s41467-022-32232-0.
4
BA.2.12.1, BA.4 and BA.5 escape antibodies elicited by Omicron infection.BA.2.12.1、BA.4 和 BA.5 逃避奥密克戎感染诱导的抗体。
Nature. 2022 Aug;608(7923):593-602. doi: 10.1038/s41586-022-04980-y. Epub 2022 Jun 17.
5
Multivariate mining of an alpaca immune repertoire identifies potent cross-neutralizing SARS-CoV-2 nanobodies.对羊驼免疫组库进行多变量挖掘，鉴定出强效交叉中和SARS-CoV-2纳米抗体。
Sci Adv. 2022 Mar 25;8(12):eabm0220. doi: 10.1126/sciadv.abm0220.
6
Analysis of antibody binding specificities in twin and SNP-genotyped cohorts reveals that antiviral antibody epitope selection is a heritable trait.在双胞胎和 SNP 基因分型队列中的抗体结合特异性分析表明，抗病毒抗体表位选择是一种可遗传的特征。
Immunity. 2022 Jan 11;55(1):174-184.e5. doi: 10.1016/j.immuni.2021.12.004.
7
Analysis of antibodies from HCV elite neutralizers identifies genetic determinants of broad neutralization.分析 HCV 精英中和抗体可鉴定广谱中和的遗传决定因素。
Immunity. 2022 Feb 8;55(2):341-354.e7. doi: 10.1016/j.immuni.2021.12.003. Epub 2022 Jan 5.
8
Discovery of ultrapotent broadly neutralizing antibodies from SARS-CoV-2 elite neutralizers.从 SARS-CoV-2 精英中和抗体中发现超强广谱中和抗体。
Cell Host Microbe. 2022 Jan 12;30(1):69-82.e10. doi: 10.1016/j.chom.2021.12.010. Epub 2021 Dec 18.
9
Human immune diversity: from evolution to modernity.人类免疫多样性：从进化到现代。
Nat Immunol. 2021 Dec;22(12):1479-1489. doi: 10.1038/s41590-021-01058-1. Epub 2021 Nov 18.
10
The PRIDE database resources in 2022: a hub for mass spectrometry-based proteomics evidences.PRIDE 数据库资源在 2022 年：一个基于质谱的蛋白质组学证据的中心。
Nucleic Acids Res. 2022 Jan 7;50(D1):D543-D552. doi: 10.1093/nar/gkab1038.