Endogenous T-Cell Responses Have Higher RE Than Vaccine-Elicited Responses

<div><p>CTL clones representing different tetramer-positive populations in each patient expressing different VB were assayed for lysis of T2 cells pulsed with various dilutions of G209n, G209–2M, M27, or M26 peptides in ⁵¹Chromium release cytotoxicity assays as described in <a href="http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.0010028#pmed-0010028-g004" target="_blank">Figure 4</a> legend. A RE score was attributed to each clone equal to the negative log₁₀ of the peptide concentration that resulted in 40% lysis of peptide-pulsed T2 cells.</p> <p>(A and B) RE scores for both (A) MART-specific and (B) gp100-specific clones from all patients were correlated with efficiency in lysing melanoma cells. Correlation coefficients were 0.66 for MART-specific clones and 0.81 for gp100-specific clones.</p> <p>(C–F) Comparison of RE scores for endogenous (patients 461 and 132) and vaccine-induced (patients 517, 520, 422 and 476) responses.</p> <p>(C and D) RE analysis with native peptides (C) M27 and (D) G209n. Mean RE (weighted) for each response is indicated with horizontal bars. Weighted means were based on all clones, not only those assayed, and were estimated by summing the RE of each analyzed clone multiplied by the number of total clones expressing the same VB, in each patient. Weighted means were as follows: patient 517, 5.7; patient 520, 7.0; patient 461, 7.9; patient 422, 9.7; patient 476, 9.9; and patient 132, 11.2. One-tailed T-tests demonstrated that endogenous responses had significantly higher RE than vaccine-induced responses: patient 461 versus patient 517, <i>p</i> = 1.8 × 10⁻⁵; patient 461 versus patient 520, <i>p</i> = 1.1 × 10⁻³; patient 132 versus patient 422, <i>p</i> = 6 × 10⁻⁶; and patient 132 versus patient 476, <i>p</i> = 4.3 × 10⁻⁴.</p> <p>(E and F) RE analysis with heteroclitic peptides (E) M26 and (F) G209–2M. Weighted means were as follows: patient 517, 10.6; patient 520, 11.1; patient 461, 11.2; patient 422, 10.5; patient 476, 11.6; and patient 132, 11.3.</p>