Figure 4.

Impact of TIGIT engagement on NK cell CD16‐mediated and natural cytotoxicity. (a) The range of TIGIT expression on NK cells (49.8−90.0%) from PLWH selected for functional studies is depicted (median ± IQR 76.6 ± 19.6%). (b) NK cells were triggered to lyse P815 cells using anti‐CD16, and the overall effect of NK cell TIGIT cross‐linking was measured using IgG₁ isotype control (not depicted) or anti‐TIGIT (represented by the yellow antibody). Percent specific lysis of P815 cells mediated through CD16 with either IgG₁ or anti‐TIGIT was compared. Wilcoxon signed‐rank test *P = 0.0351. (c) NK cells were pretreated with anti‐TIGIT to prevent interaction with PVR on K562 cells, and lysis was measured and compared with lysis mediated by NK cells pretreated with IgG₁. Student's paired t‐test ****P < 0.0001. Percent increase in NK cell cytotoxicity against K562 targets in the presence of anti‐TIGIT vs IgG₁ was calculated from raw data in (c) and compared between (d) groups distinguished by CMV serostatus (Mann–Whitney U‐test *P = 0.0309) and (e) correlated with percentage of FcRγ^– NK cells. (f) Absolute increase in NK cell lysis of K562 cells in the presence of anti‐TIGIT mAb was correlated with the percentage of TIGIT⁺ NK cells. For all graphs, filled symbols represent CMV‐seronegative (n = 10) participants, and open symbols depict CMV‐seropositive participants (n = 16). Horizontal lines bisecting groups in a and d represent median with IQR.