The Immunology Core of the TBRU is led by John Altman. With his group at the Emory Vaccine Center and their expertise in MHC tetramer technology, development of advanced flow cytometry methods, and development of novel viral vector antigen delivery systems for in vitro T cell assays, and along with the collaboration of Alessandro Sette's group at the La Jolla Institute of Allergy and Immunology and their expertise in epitope mapping, application of MHC peptide binding algorithms, and HLA typing, the Immunology Core of the TBRU will be able to perform the most sophisticated-to-date analyses of the phenotypes of T cell responses to Mycobacterium tuberculosis (Mtb) in humans (Projects 1 and 2) and rhesus macaques (Project 3). The activities of the Immunology Core include both provision of centralized standard support services and reagents, as well as development of important novel reagents and research activities. Standard support services include provision of MHC typing in humans and rhesus macaques; maintenance and distribution of peptide libraries;and construction, validation, and distribution of MHC tetramers, all to be used by every TBRU project. Innovative research activities include application of a viral antigen delivery system that will enable screening of more than 60 Mtb antigens for T cell responses in rhesus macaques, development of novel cell lines and MHC tetramer reagents for mapping epitopes and their MHC restriction elements, and application of CyTOF mass cytometry technology?including the use of mass-tagged MHC tetramers?^to enable multiparametric descriptions of Mtb-specific T cells that will be tested for their use as biomarkers indicative of defined disease and infection states.
The current diagnostic tests for Mtb exposure are uni-dimensional and fail to both differentiate between distinct clinically significant disease states and to enable prediction of which positive subjects are most likely to develop active disease. The Immunology Core will seek to develop tools to enable multi-dimensional characterization of Mtb-specific T cells and explore the predictive power of these characteristics.
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