The PD-1 Reagent Core, Core B, provides a critical means by which the PPG will achieve its goals of understanding how to therapeutically manipulate the negative second signals provided by PD-1 and its ligands and the mechanism of these inhibitory signals. Core B will coordinate the use of mAb, Ig fusion proteins and transgenic technology to enable the study of the role of PD-1 and its ligands in regulating immune responses to HIV and LCMV.
Our specific aims are: 1) To generate novel monoclonal antibodies and Ig fusion proteins to study the function and expression of PD-1/PD-1 Ligand pathway members; 2) To generate transgenic and knockout mice to study PD-1 signaling and the regulation of PD-1 expression;and 3) To serve as a repository that will maintain and produce existing and newly generated mAbs and Ig fusion proteins, and transgenic and knockout strains for PPG investigators. The availability of large quantities of mAbs and Ig fusion proteins is critical to the success of Projects 1-4. Ig fusion proteins, via binding to their ligand, will visualize ligand-expressing cells and may act as agonists via cross-linking and transducing signals through receptors. MAbs will be used to visualize the expression of PD-1/PD-1 Ligands and as pathway agonists and antagonists. The generation of conventional and conditional transgenic and knockout PD-1 mutant mouse strains will facilitate analyses of the in vivo regulation of PD-1 gene expression and a mechanistic understanding of PD-1 signaling in vivo. The production of these critical reagents by a core will be time and cost efficient, and provide standardized reagents that will facilitate comparison of data by investigators in this PPG.
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