It is widely accepted that PD-1 suppresses TCR signaling.[43] However, CD28 has also been proposed as the primary target of PD-1.[8] In parallel, another study showed that CD28 signaling on exhausted T cells in mice is required for anti-PD-L1 therapies to eliminate cancer cells and viral infections efficiently,[44] but how PD-1 specifically modulates CD28 versus TCR signaling remains to be determined. This evidence concerns the gene CD28 and viral infectious disease.