IMMUNOBIOLOGY Enumeration of human antigen–specific naive CD8 T cells reveals conserved precursor

CD8 T cells is believed to be important in the shaping of adaptive immune re-sponses, and is predictive for the magni-tude of priming responses in mouse mod-els. Because of extremely low precursor frequencies, knowledge about these cells comes from indirect techniques and esti-mations. Here, we present a strategy based on the combination of tetramer staining, magnetic-bead enrichment, and multiparametric cytometry, which permit-ted direct detection and analysis of CD8 T cells reactive for 6 different naive epitopes (MART-126-35, HIV-1 Gag p1777-85, hepatitis C virus [HCV] NS31406-1415, HCV Core132-140, NY-ESO-1157-165, and cytomeg-alovirus [CMV] pp65495-503). Interestingly, we detected higher than 100-fold differ-ences in precursor frequency across these epitopes (from 0.6 106 to 1.3 104), but conserved frequencies among humans. Development of a proce-dure for direct assessment of T-cell pre-cursor frequency in humans has impor-tant implications, with particular relevance to vaccine development and monitoring of tumor and self-reactive T cells. (Blood. 2010;115(18):3718-3725