Core C: Humoral and Serological Core

项目摘要 该U19的一个主要目标是确定PD-1阻断如何影响针对PD-I的人抗体应答。 不同的病毒抗原核心C将全面询问针对一系列不同抗体的血清抗体应答。 在项目1和2中，来自接受PD-1治疗的供体的病毒。核心将标准化分析，完成 分析，并为复杂的血清学数据集的分析提供计算支持。我们将提供 基于ELISA的标准化服务，量化与项目相关的5种病毒的特异性抗体 1和2.我们还将通过测定相对亲和力的ELISA评估抗体应答的质量， 同种型多样性PD-1阻断可能以更微妙或更全面的方式影响抗病毒抗体应答。 的方式为了解决这个问题，我们将完成血清学筛查，以检查PD-1阻断如何影响抗体 对大部分已知的人类病毒的反应。为此，我们将使用一种新的基于阵列的检测方法，称为 “Virosan”，其测量抗体与> 400，000个非冗余病毒肽的结合。我们还将提供 集中分析针对单一病毒（流感）的抗体反应的服务。所有的人类都是 在儿童时期接触流感病毒和所有成年人接触流感都涉及回忆 记忆B细胞和从头B细胞反应的刺激。我们的流感病毒抗原分析将 允许我们确定PD-1阻断是否差异调节从头与记忆抗体应答。 这些标准化服务将共同实现血清样本的完整抗原表征 项目1和2。

Project Summary A major goal of this U19 is to determine how PD-1 blockade affects human antibody responses against different viral antigens. Core C will fully interrogate serum antibody responses against a range of different viruses from donors undergoing PD-1 therapy in Projects 1 and 2. The Core will standardize assays, complete assays, and provide computational support for the analyses of complex serological datasets. We will offer standardized ELISA-based services that quantify antibodies specific for 5 viruses that are relevant for Projects 1 and 2. We will also assess quality of antibody responses through ELISAs that measure relative affinities and isotype diversity. It is possible that PD-1 blockade affects antiviral antibody responses in more subtle or global ways. To address this, we will complete serological screens to examine how PD-1 blockade affects antibody responses to a large fraction of known human viruses. For this, we will use a new array-based assay, termed ‘Viroscan’, that measures antibody binding to >400,000 non-redundant viral peptides. We will also offer services that intensively analyze antibody responses against a single virus (influenza). All humans are exposed to influenza virus in childhood and all adult encounters with influenza involve both the recall of memory B cells and the stimulation of de novo B cell responses. Our influenza virus antigenic analyses will allow us to determine if PD-1 blockade differentially regulates de novo versus memory antibody responses. Together, these standardized services will allow for the complete antigenic characterization of serum samples for Projects 1 and 2.