The contractor will apply innovative, highly-multiplexed DNA-barcoded antigen assays to comprehensively discover and validate 100,000s of CD4 T cell epitopes across the entire proteome of Mycobacterium Tuberculosis (Mtb) – together with their HLA restrictions, cognate paired TCR α:βs, and corresponding T cell transcriptomes . The Assays will focus on a large panel of HLA proteins that include alleles prevalent in sub-Saharan African populations with high disease burdens but that remain vastly understudied at the epitope level. By comparing cohorts with different disease states across a large two-dimensional space defined by the pathogen genome and host transcriptome, the contractor will identify novel T cell features associated with protection from disease.