Recent studies have strongly implicated natural killer (NK) cells in control of M.tb infection. NK cell function is regulated by the interaction of the killer cell immunoglobulin-like receptors (KIR) and their HLA class I ligands. Both are highly polymorphic and diverse in the variants that characterize human populations. We have developed a sensitive high-throughput sequencing and bioinformatics protocol targeted to HLA and KIR genes, which we will use to analyze all 10,000 individuals in the TB case-control study. With this high-resolution data, we expect to identify subsets of KIR and HLA alleles that predispose to development of active TB. We will also apply a novel interaction score that we developed using experimental data, to measure NK cell strength per individual.