Single Naive CD4+ T Cells from a Diverse Repertoire Produce Different Effector Cell Types during Infection

•Individual naive CD4+ T cells have unique effector differentiation potentials•The diverse progeny of clones average to produce a consistent effector cell pattern•TCR signal amount helps dictate cell-mediated versus humoral immunity•Small CD4+ T cell repertoires produce different types of immunity between animals

SummaryA naive CD4+ T cell population specific for a microbial peptide:major histocompatibility complex II ligand (p:MHCII) typically consists of about 100 cells, each with a different T cell receptor (TCR). Following infection, this population produces a consistent ratio of effector cells that activate microbicidal functions of macrophages or help B cells make antibodies. We studied the mechanism that underlies this division of labor by tracking the progeny of single naive T cells. Different naive cells produced distinct ratios of macrophage and B cell helpers but yielded the characteristic ratio when averaged together. The effector cell pattern produced by a given naive cell correlated with the TCR-p:MHCII dwell time or the amount of p:MHCII. Thus, the consistent production of effector cell subsets by a polyclonal population of naive cells results from averaging the diverse behaviors of individual clones, which are instructed in part by the strength of TCR signaling.

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