Inhibitors of TLR9 or its downstream signaling block the capsid-specific CD8⁺T-cell response. (A) Experimental timeline. TLR9i, MyD88i, pyrrolidine dithiocarbamate, or PBS were IV co-injected with 1 × 10¹¹ vg AAV2-SIINFEKL into WT C57BL/6 mice. (B) Tetramer-positive CD8⁺ T cells were quantified over time in peripheral blood (n = 4/group). (C) Anti-AAV2 immunoglobulin 2c antibodies were quantified by enzyme-linked immunosorbent assay 2 months post-injection. (D) Cartoon indicating specific targets of the TLR9 signaling pathway blocked by the small molecule inhibitors and antibody used in this study. Data points are averages ± SEM. Statistical comparisons are made relative to mice that received only vector in PBS. ns, not significant; PDTC, pyrrolidine dithiocarbamate.