CD8⁺ TCR signaling is intact when stimulated under hypoxia, but stimulation-induced mTOR activity and c-Myc upregulation are impaired. CD8⁺ T cells were cultured for 16 hours at 21% or 1% O₂, stimulated via CD3/CD28 at these oxygen tensions as indicated, as assessed for intracellular abundance of (A) phospho-Lck (p-Lck) after 15 minutes, (B) phospho-Erk (p-Erk) after 1 hour, (C) phospho-Akt (p-Akt), (D) phospho-mTOR (p-mTOR), and (E) phospho-p70S6 kinase (p-p70S6K) all after 24 hours, and (F) total c-Myc after 48 hours (summarized for n = 5-8 independent donors, shown as [A-B] mean fluorescence intensity [MFI], [C-F, upper] normalized to the average [mean] MFI for the 4 matched samples from each donor, or as stimulation-induced change [Δ], calculated as MFI of stimulated sample/MFI of matched unstimulated sample at each oxygen tension). P values were calculated by 2-way ANOVA and Holm-Sidak’s post hoc test or (lowest line) paired t test. ∗P < .05, ∗∗P < .01, ∗∗∗P < .001.