How t cells do the "search for the needle in the haystack"

Abstract

In the body, a T cell is confronted with millions of antigen-presenting cells (APCs) in the search for potentially harmful antigen. To elicit an appropriate immune response, this search has to be performed as fast and as precise as possible. These two requirements, however, are at odds with each other: fast searches lack accuracy, whereas high fidelity decisions are typically time-consuming. Here, we use the archetypical search for the needle in the haystack as an analogy for the T cell's search problem. We provide a statistical framework to quantitatively estimate the constraints of search strategies for rare instances. Particularly, we propose a solution for balancing the demand for high speed with low error rates. It takes advantage of a two-phase search process, which combines a first rapid scan with a second high-fidelity check. Finally, we provide arguments that support a two-phase search model for identification of antigen-positive APCs by T cells.