A pool of T cells responding to a given antigen differentiates into a mixture of qualitatively distinct kinds of effector T cells. In Cell, Jenkins and colleagues track the progeny of individual T cells to determine the signals that give rise to three different effector fates: TH1, TFH or germinal center TFH (GC-TFH). A pool of responding T cells produces a characteristic proportion of TH1 cells, TFH cells and GC-TFH cells that depends on the type of experimental bacterial challenge and dose of the challenging antigen. Single naive T cells give rise to a distinct pattern of effector cells; however, averaging the response of all the potential responder cells results in a ratio of effector cells characteristic of the particular antigenic challenge. The fate of a given cell depends at least in part on the strength of signaling via the T cell antigen receptor, which thus has a key instructive role in determining the fate of effector cells.

Cell 153, 785–796 (2013)