{Reference Type}: Journal Article
{Title}: Structural basis for the immune recognition and selectivity of the immune receptor PVRIG for ligand Nectin-2.
{Author}: Hu S;Han P;Wang M;Cao X;Liu H;Zhang S;Zhang S;Liu J;Han Y;Xiao J;Chen Q;Miao K;Qi J;Tan S;Gao GF;Wang H;
{Journal}: Structure
{Volume}: 32
{Issue}: 7
{Year}: 2024 Jul 11
{Factor}: 5.871
{DOI}: 10.1016/j.str.2024.03.012
{Abstract}: Nectin and nectin-like (Necl) co-receptor axis, comprised of receptors DNAM-1, TIGIT, CD96, PVRIG, and nectin/Necl ligands, is gaining prominence in immuno-oncology. Within this axis, the inhibitory receptor PVRIG recognizes Nectin-2 with high affinity, but the underlying molecular basis remains unknown. By determining the crystal structure of PVRIG in complex with Nectin-2, we identified a unique CC' loop in PVRIG, which complements the double-lock-and-key binding mode and contributes to its high affinity for Nectin-2. The association of the corresponding charged residues in the F-strands explains the ligand selectivity of PVRIG toward Nectin-2 but not for Necl-5. Moreover, comprehensive comparisons of the binding capacities between co-receptors and ligands provide innovative insights into the intra-axis immunoregulatory mechanism. Taken together, these findings broaden our understanding of immune recognition and regulation mediated by nectin/Necl co-receptors and provide a rationale for the development of immunotherapeutic strategies targeting the nectin/Necl axis.