Abstract:
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.
摘要:
抗体和T细胞受体(TCR)是适应性免疫的基本组成部分。系列规模的功能来自它们的表位结合特性,就像温度这样的宏观特性来自微观分子特性一样。然而,大多数方法来进行量表测量,包括序列多样性和熵,不是以这种方式基于抗体或TCR功能。因此,他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,根据其组成抗体和TCR的表位结合特性来描述库,基于对数千种抗体-抗原和TCR-肽-主要-组织相容性-复合物结合相互作用以及超过400种高通量组库的分析。我们表明,组库由具有相似结合特性的松散重叠类别的抗体和TCR组成。我们展示了该框架区分特定响应与特定响应的潜力。流感疫苗接种者的旁观者激活,对巨细胞病毒(CMV)感染的队列进行分层,并确定潜在的免疫学“超级老人”。“类增加了一个有价值的维度来评估免疫功能。