TCR repertoire diversity maps in HIV-infected and -uninfected subjects. (A-B) Plots represent the T cells present in 1.5 mL of blood, with each color block representing a different subpopulation. The x-axis represents the numbers of cells; and y-axis, TCR repertoire diversity (number of unique sequences found in the cell sample). We calculated this using several simplifying assumptions. First, we assumed that all receptors were present at equal frequency within a given T-cell subpopulation. Based on the results of our diversity measurements of highly diverse naive samples, we estimated that the maximal measurable diversity in a sample of n cells was n/2.5. Finally, we assumed that, if the number of a specific subpopulation of cells in a 1.5-mL blood volume was close to the diversity of that population, the actual diversity seen in 1.5 mL would be reduced because of sampling, according to the Poisson distribution. We therefore plotted the diversity of each subpopulation as the smallest of the 3 values: n/2.5; d; or [(n/2.5)⁺d)/3], where n = number of cells of that subpopulation in a 1.5-mL blood volume and d = maximum measured sequence diversity of that subpopulation in a sample of any size. Sequences within subpopulations are depicted as nonoverlapping; sequencing experiments suggest that this is largely the case with clone nucleotide sequences^32,–34  but was not directly verified in our study. Dashed lines indicate total cell number and total TCR repertoire diversity within the 1.5-mL blood sample. The 2 plots are for representative subjects from the prespecified comparison group who are either HIV-uninfected (A) or HIV-infected (B). Plots for all subjects in the prespecified comparison groups are available as supplemental data. All plots use identical scales for cell number and TCR diversity. (C) Correlation between subpopulation and sum blood measurements. For all subjects in the prespecified comparison group, the measured sum TCR repertoire diversity in whole blood (expressed in relative Cot units, as in Figure 2) is shown on the x-axis. Subpopulation TCR repertoire diversity values (sequences expected per 1.5 mL whole blood), plotted on the y-axis, were calculated as the sum of each of the absolute values of the T-cell subpopulations that could be evaluated. The r² value was 0.72 (P < .0001).