Immune bet-hedging: how to make diverse memories to prepare for future challenges

Following immune activation, CD4 T cells that are specific to the pathogen's peptides proliferate into effector cells, before decaying back into memory cells, which help keep protection against future challenges. It has been proposed that the depletion of peptides, which are necessary for sustained proliferation, is the main cause of decay. However, experiments suggest another cause: the active inhibition of T cells by each other, which primarily affects the most proliferative ones. We show that this second phenomenon limits the ``rich gets richer'' effect of proliferative growth, resulting in a more diverse memory repertoire. We argue that this diversity helps cover a larger fraction of future pathogens that differ by one point mutation in their peptide (escape mutants), and present preliminary data to support this picture.