Modeling Killer Cell Migration And Search Strategies

During the immune response, cytotoxic T lymphocytes (CTL) and Natural Killer cells (NK cells) patrol the human body. Upon recognition of virus-infected or cancerous target cells, the killer cells release lytic granules at the immunological synapse and kill the targets. For optimal immune function, the migration machinery has to be adjusted in order to maximize the search efficiency. We used in vitro time lapse microscopy on primary human CTL and NK cells to study their migration in a two-dimensional geometry. In the absence of target cells, CTL alternate between a mobile and a stationary state. The preference for each state depends on the external calcium concentration. On a short time scale (seconds/minutes), killer cell migration is characterized by directional persistence, while migration on a longer time scale (minutes/hours) is random. A mathematical model of a persistent random walker can accurately describe killer cell migration and reveals an optimum for target search efficiency. This optimum depends on the length of persistent motion in one direction and the size of the search space. We believe that this model is very useful to understand how regulation of killer cell migration can serve to optimize the immune response.