Interpreting T-cell search "strategies" in the light of evolution under constraints

Inge M. N. Wortel, Johannes Textor

Abstract: Author summary T cells are immune cells with an astounding ability to move nearly anywhere in the body. This motion helps them detect and clear up pathogens, and understanding it is key to understanding T-cell immunity. Importantly, the continuous search for pathogens means that T cells face different challenges throughout their lifetime: their needle-in-a-haystack quest for the first signs of disease in lymph nodes differs greatly from their motion in an infected lung, or from how they patrol the skin to guard against future reinfections. These observations have raised the intriguing question: have years of evolution equipped T cells with distinct search “strategies”, optimized for whichever searching tasks they might encounter? Although several studies have addressed this question in mathematical models, to date, none have explicitly considered the evolutionary process itself. Here, we directly simulate evolutionary optimization of T-cell search. We find that explicitly simulating “survival of the fittest searchers” can shed new light on why T cells move the way they do. Importantly, we find that the evolving movement patterns are only in part optimized “strategies”—while other parts may merely be “side effects” stemming from the constraints arising from the cell’s molecular motor acting in a maze-like environment.