Tuberculosis causes a large number of deaths worldwide, as well as contributing to morbidity and reduced quality of life. Most prominent in economically underdeveloped countries, the disease is currently posing an increasing challenge to the western world due to incresed travel activity combined with the increasing occurrence of multiresistant strains of Mycobacterium tuberculosis. Currently available vaccination regimens have proven insufficient to eradicate the disease. Mycobacteria pose a special chall enge to the immune system. M. tuberculosis can reside for years inside host cells, before awaking to cause disease in immunocompromised individuals. In this latent state, humoral vaccines are not effective. Thus, new vaccination strategies that induce lon g-lasting, efficient cellular immunity are highly warranted. We have for many years studied natural killer (NK) cells, focusing on their ability to recognize cells that have undergone intracellular infection or malignant transformation. NK cells can recog nize and kill cells that are infected with parasites, virus or bacteria. Importantly, NK cells kill macrophages infected with M. tuberculosis. The present project is aimed at identifying the receptors that NK cells use to detect infection. Increased knowl edge about the role of NK cells in combating infection may provide a new approach to inducing protective immunity, given the recently demonstrated ability of NK cells to maintain immunological memory and form NK memory cells.