PROJECT SUMMARY: Clinical Core The Clinical Core (CC) is an integral part of the LJI HIPC Program. The Core provides leadership and management of all clinical samples and data. This includes ensuring all regulatory documentation is in place for human subjects research both at LJI and at collaborators' institutions, appropriate training of personnel and monitoring all clinical study activities of the HIPC center, managing oversight of internal and external sample collection which includes arranging for regular shipments of samples to LJI, sample storage, clinical data collection, oversight in our specialized donor record administrative system DoRAS, and QC of received samples. The CC ensures that HLA typing is performed on all samples that require it, as well as ensuring it works with the Projects, Sequencing, and Data Management and Analysis Cores to confirm sample integrity and identity throughout the experimental and bioinformatics pipeline process. The overall scientific program will develop a series of immune signatures for antigen-specific T cells responding to a diverse range of respiratory pathogens, such as SARS-CoV-2, common cold coronaviruses, influenza, tuberculosis, pneumococcus, pertussis, and fungi (aspergillus and candida). The success of the entire program is contingent upon successful accrual of high-quality human samples and the associated donor information. Obtaining such samples in sufficient quantity and quality presents specific challenges, because of the proposal's focus on comparison of T cells reactive to different respiratory pathogens, and enrollment of individuals from several, very different, geographical locations. To address these challenges, the CC will use well-developed and validated methods to procure samples (including PBMC, lung tissue, and BAL) from cohorts associated with natural infection, ongoing disease, and vaccination. The cohorts to be used for this program will be obtained from either our well-established in-house LJI Center for Clinical Investigation (CCI) or our experienced collaborators and clinicians that have access to unique cohorts and with whom we have enjoyed fruitful relationships over many years. We are confident in our ability to provide the necessary samples as well as clinical and scientific input to enable the most robust and compelling studies. We will continue recruitment and sample acquisition of already established cohorts, and access previously obtained samples in the context of the SARS-CoV-2 project (Project 1). In addition, we have established long-standing relationships with Drs. Dharshan DeSilva (Sri Lanka), Matt O'Shea (UK), Maria Lerm (Sweden), Cesar Ugarte (Peru), and Richard Silver (USA) that will provide longitudinal samples from subjects with latent TB infection or who are diagnosed with active TB, and from subjects undergoing BCG vaccination (Project 2). The CC will provide lung tissue and bronchoalveolar lavage specimens (BAL) from patients undergoing lung surgery fo...