C-restricted CTLs have potent antiviral activity against HIV-1 and are unaffected by Nef-mediated HLA down-regulation. (A) CTL clones KS7 (Env specific, B*07 restricted) and SE7/126E (Env specific, C*15 restricted) were compared for their abilities to inhibit HIV-1 with wild-type or deleted Nef. The target cells were primary CD4⁺ T lymphocytes from a seronegative B*07⁺/C*15⁺ donor, and the assay was otherwise performed as in Figure 1. The potent level of inhibition of replication seen here for clone SE7/126E (and clone S16-RY11-10.41 in Figure 1) was typical of multiple experiments with HLA-C–restricted CTL clones. (B) Nef effects on the A- and B-restricted CTL epitopes shown in Figure 3 were compared to several C-restricted clones (listed in Table 1) that were tested and summarized in the same manner. The values for the A- and B-restricted CTLs versus the C-restricted CTLs were significantly different (2-tailed t test, P < .001). MEAN A/B indicates the average of results from HLA-A– and -B–restricted epitopes, and MEAN C indicates the average of results from HLA-C–restricted epitopes. Error bars represent the standard deviation for all A/B- or C-restricted CTLs.