CORE SUMMARY The Mutant Mouse Core (Core B) is an essential core that will be used extensively by all three projects. Given the complex interplay between different inhibitory receptors on multiple cell types, the only way one can dissect these critical disease-related biological questions in vivo is with sophisticated mouse models. A significant strength of this PPG application is the unique `immunological toolbox' that it will utilize, specifically PD1/LAG3 floxed mice combined with a unique collection of lineage-specific, and in most instances temporally controlled, Cre recombinase-expressing mice. These tools will give us unprecedented control and thus insight into PD1/LAG3 synergy and function in multiple cell types. AIM 1: To provide required PD1/LAG3 mutant mice. The Core will be administered from the University of Pittsburgh (Pitt), with the majority of the mutant mouse breeding and procurement outsourced to Taconic under Murine Pathogen Free barrier conditions identical to the majority of their commercial breeding practices. Taconic will deliver mice to all research sites on a rotating bi-weekly basis using their conventional delivery mechanism, thereby avoiding lengthy quarantine. AIM 2: To generate new mutant mouse combinations. The Core will generate new mutant mouse combinations that introduce different genetic elements such as new Cre stains. PPG Interactions: Core B will support Project 1, Project 2 and Project 3 extensively, and interact with Core A to provide easy access to breeding, shipping and genotyping data. Core B will also perform additional crosses to generate any strain combinations required by the projects. Core B will interact with Core A to provide easy access to breeding, shipping and genotyping data and ongoing monitoring.