All blood samples were obtained from individuals seronegative for HIV and CMV exposures. HSV exposure is as indicated (naïve vs exposed). (A) Frequencies of tetramer tagged cells per million CD4+ T cells. Each symbol represents an antigen-specific population from one individual and the bar indicates the mean of experiments performed independently using blood obtained at different times. (B) Comparison between T cells recognizing a novel foreign antigen (pre: HIV-1, CMV, HSV-naïve), exposed foreign antigen (post: Flu, tetanus, HSV-exposed), and self antigen (self: Fib, gp100, PPins). Figure summarizes data from all 26 individuals. (C) Precursor frequencies of self-specific lymphocytes that recognized gp100, Fib, or PPins in people ages <40 (n= 7), 40–60 (n = 13), >60 (n = 6). (D) Precursor frequency of self-specific lymphocytes that recognized gp100, Fib, or PPins in males (n = 17) and females (n = 9) (See also Fig. S2).