Division of Clinical Pathology, Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA 02215.
Division of Clinical Informatics, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA 02215.
Proc Natl Acad Sci U S A. 2022 Aug 23;119(34):e2203505119. doi: 10.1073/pnas.2203505119. Epub 2022 Aug 15.
Antibodies and T cell receptors (TCRs) are the fundamental building blocks of adaptive immunity. Repertoire-scale functionality derives from their epitope-binding properties, just as macroscopic properties like temperature derive from microscopic molecular properties. However, most approaches to repertoire-scale measurement, including sequence diversity and entropy, are not based on antibody or TCR function in this way. Thus, they potentially overlook key features of immunological function. Here we present a framework that describes repertoires in terms of the epitope-binding properties of their constituent antibodies and TCRs, based on analysis of thousands of antibody-antigen and TCR-peptide-major-histocompatibility-complex binding interactions and over 400 high-throughput repertoires. We show that repertoires consist of loose overlapping classes of antibodies and TCRs with similar binding properties. We demonstrate the potential of this framework to distinguish specific responses vs. bystander activation in influenza vaccinees, stratify cytomegalovirus (CMV)-infected cohorts, and identify potential immunological "super-agers." Classes add a valuable dimension to the assessment of immune function.
抗体和 T 细胞受体 (TCR) 是适应性免疫的基本组成部分。其表位结合特性决定了其 repertoire-scale 功能，就像温度等宏观性质源于微观分子性质一样。然而，大多数 repertoire-scale 测量方法，包括序列多样性和熵，都不是基于抗体或 TCR 以这种方式的功能。因此，它们可能忽略了免疫功能的关键特征。在这里，我们提出了一个框架，根据数千个抗体-抗原和 TCR-肽-主要组织相容性复合物结合相互作用以及 400 多个高通量 repertoire 的分析，根据其组成抗体和 TCR 的表位结合特性来描述 repertoire。我们表明 repertoire 由具有相似结合特性的松散重叠的抗体和 TCR 类组成。我们证明了该框架在流感疫苗接种者中区分特异性反应与旁观者激活、分层巨细胞病毒 (CMV) 感染队列以及识别潜在免疫“超级年龄”方面的潜力。类别为评估免疫功能增加了一个有价值的维度。
