The CD8+ T Cell Response to Infection is Dominated by the Progeny of Few Naïve T Cells (110.12)

Abstract Following infection, antigen-specific CD8+ T cell numbers increase dramatically. Analysis of antigen-specific T cell responses at the bulk cell level has provided insight into the average number of cell divisions that T cells undergo upon activation. However, it is unclear whether all naïve T cells of a given affinity for antigen produce equal numbers of progeny, or whether the total effector T cell pool is predominantly created by the output of few. To quantify how many daughter cells individual naïve T cells produce, we have generated naïve OT-I T cells harboring unique genetic tags (barcodes) and have measured the number of progeny per labeled cell by second-generation sequencing of barcode sequences after infection. Our data reveal that upon infection, individual OT-I T cells that are recruited into the response produce highly variable numbers of daughter cells. These data indicate that the bulk of pathogen protection provided by an antigen-specific T cell response is due to the progeny of only a handful of cells.