The PD-1 Reagent Core, Core B, provides a critical means by which the PPG will achieve its goals ofunderstanding how to therapeutically manipulate the negative second signals provided by PD-1 and itsligands and the mechanism of these inhibitory signals. Core B will coordinate the use of mAb, Ig fusionproteins and transgenic technology to enable the study of the role of PD-1 and its ligands in regulatingimmune responses to HIV and LCMV.
Our specific aims are: 1) To generate novel monoclonal antibodiesand 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-1expression; and 3) To serve as a repository that will maintain and produce existing and newlygenerated 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. Igfusion proteins, via binding to their ligand, will visualize ligand-expressing cells and may act as agonists viacross-linking and transducing signals through receptors. MAbs will be used to visualize the expression ofPD-1/PD-1 Ligands and as pathway agonists and antagonists. The generation of conventional andconditional transgenic and knockout PD-1 mutant mouse strains will facilitate analyses of the in vivoregulation of PD-1 gene expression and a mechanistic understanding of PD-1 signaling in vivo. Theproduction of these critical reagents by a core will be time and cost efficient, and provide standardizedreagents that will facilitate comparison of data by investigators in this PPG.
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