疫苗诱导的T细胞反应保持多克隆性，具有高抗原受体亲和力

IF 16.3 1区医学 Q1 IMMUNOLOGY

Science Immunology Pub Date : 2025-10-03 DOI:10.1126/sciimmunol.adu6730

Katharina Kocher, Felix Drost, Abel Mekonnen Tesfaye, Carolin Moosmann, Christine Schülein, Myriam Grotz, Elvira D’Ippolito, Frederik Graw, Bernd Spriewald, Dirk H. Busch, Christian Bogdan, Matthias Tenbusch, Benjamin Schubert, Kilian Schober

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引用次数: 0

摘要

克隆扩增是适应性免疫的一个标志，与动物模型相比，在人类中以标准化的方式进行研究一直具有挑战性。我们研究了一组29名健康个体，他们在突破性感染之前接受了三次针对SARS-CoV-2的mRNA疫苗接种。我们通过ELISpot表征了CD8 T细胞对16个表位特异性反应的大小、表型和克隆组成；流式细胞术;单细胞RNA、蛋白和T细胞受体（TCR）测序。来自5个表位特异性基因库的106个tcr被重新表达并测试了肽敏感性。尽管疫苗募集的T细胞库富集了高亲和度的tcr，但差异克隆扩增与亲和度的细微差异无关。相反，多克隆性的维持确保了通过改变表位抵抗病毒突变逃逸的稳健性。破译人类抗原特异性T细胞库的功能有助于我们对人类T细胞生物学的理解，并可能指导疫苗和其他免疫疗法的开发。

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Vaccination-induced T cell responses maintain polyclonality with high antigen receptor avidity

Clonal expansion is a hallmark of adaptive immunity and has been challenging to investigate in humans in a standardized manner compared with animal models. We studied a cohort of 29 healthy individuals who received three mRNA vaccinations against SARS-CoV-2 before a breakthrough infection. We characterized the magnitude, phenotype, and clonal composition of CD8 T cell responses against 16 epitope specificities by ELISpot; flow cytometry; and single-cell RNA, protein, and T cell receptor (TCR) sequencing. One hundred six TCRs from five epitope-specific repertoires were reexpressed and tested for peptide sensitivity. Whereas vaccination-recruited T cell repertoires were enriched for high-avidity TCRs, differential clonal expansion was not linked to fine avidity differences. Instead, maintenance of polyclonality ensured robustness in counteracting viral mutational escape through altered epitopes. Deciphering the functionality of human antigen-specific T cell repertoires instructs our understanding of human T cell biology and may guide the development of vaccines and other immunotherapies.

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来源期刊

Science Immunology Immunology and Microbiology-Immunology

CiteScore

32.90

自引率

2.00%

发文量

183

期刊介绍： Science Immunology is a peer-reviewed journal that publishes original research articles in the field of immunology. The journal encourages the submission of research findings from all areas of immunology, including studies on innate and adaptive immunity, immune cell development and differentiation, immunogenomics, systems immunology, structural immunology, antigen presentation, immunometabolism, and mucosal immunology. Additionally, the journal covers research on immune contributions to health and disease, such as host defense, inflammation, cancer immunology, autoimmunity, allergy, transplantation, and immunodeficiency. Science Immunology maintains the same high-quality standard as other journals in the Science family and aims to facilitate understanding of the immune system by showcasing innovative advances in immunology research from all organisms and model systems, including humans.