Antibody Cooperation mediated by Fc-gamma Receptor (FcyR)-bearing cells

项目2. Fc-Fc-γ受体（FcγR）介导功能的抗体协同作用。 尽管人和RM之间存在Fc-FcR相互作用的内在差异，但我们假设， 两个物种之间在Fcγ R携带细胞接合方面的相似性可定义为1） 选择具有FcγR基因型/表型介导抗病毒功能的RM，这些基因型/表型与 人;和2）通过高度选择性的Fc- FcγR抗体相互作用，可协同作用以招募与人类相似的携带Fc γ R的细胞 总体计划假设是，RM模型可以得到实质性改进，用于检测基于抗体的 通过阐明影响物种特异性FcgR依赖性的关键变量， 效应子功能（即抗体表位特异性，免疫复合物形成，同种型/亚类，糖基化， 和FcR基因型/表型。 项目2的具体目标如下： AIM 1.定义RM和RM之间FcγR介导的Ab效应子功能的相似性和差异 人类 AIM 2.确定能够共同介导上级抗病毒功能的抗体组合

Project 2. Antibody Cooperation for Fc-Fc-gamma Receptor (FcγR)-mediated functions. Although intrinsic differences in Fc-FcR interactions exist between humans and RM, we hypothesize that similarities between the two species for engagement of the FcγR-bearing cells can be defined to 1) select RM with FcγR genotypes/phenotypes mediating antiviral functions that match those observed in humans; and 2) identify combinations of antibodies of multiple specificities, through highly selective Fc- FcγR antibody interactions, that can act in concert to recruit Fc-gamma R-bearing cells similar to humans The overall Program hypothesis is that the RM model can be substantially improved for testing antibody-based interventions and vaccines through elucidation of key variables that impact species-specific FcgR-dependent effector functions (i.e. antibody epitope specificity, immune complex formation, isotype/subclass, glycosylation, and FcR genotype/phenotype. The specific aims for Project 2 are as follows: AIM 1. Define similarities and differences in FcγR mediated Ab effector function between RM and humans. AIM 2. Determine the combination of antibodies that together can mediate superior antiviral function