CORE SUMMARY The overall goal of this PPG application is to develop a mechanistic understanding of the cellular and molecular basis for PD1 and LAG3 interactions that regulate T cell function in autoimmunity, cancer and chronic viral infections. Core D will provide sophisticated and relevant technologies and expertise to PPG investigators for understanding how the interplay between PD1 and LAG3 affects cellular interactions and relevant molecular pathways in intact experimental tissues from mice with autoimmune disease (Project 1), cancer (Project 2) and chronic viral infection (Project 3). The Aims of this Core are: AIM 1: To provide basic expertise and technologies for detailed immunopathologic tissue analysis; AIM 2: To apply high- resolution quantitative, correlative immunopathology using highly-multiplexed cyclic immunofluorescence (t- CyCIF); and AIM 3: To maintain an annotated biospecimen bank/archive for future studies. These data will interface with data generated by Core C and PPG projects in order to develop protocols to visualize new molecules, as well as metrics generated from conventional histology (e.g., qualitative assessment and grading of lesion severity) and clinical parameters (e.g. survival and weight loss). Core D will interact extensively with all three Projects, with Core A for oversight and administrative support, and Core C by developing new staining protocols for cellular and histologic investigation of key genes and their products that Core C determines are regulated by PD1 and LAG3.