English: This figure represents the findings in Kondo et al., 2025, Front Immunol 16:1573492, doi: 10.3389/fimmu.2025.1573492.

(A) Presence of PD-1, its ligands PD-L1 and PD-L2, and the phosphatases SHP-1, SHP-2, and SHP-2-like (SHP-2L) in representative jawed vertebrates, including sharks, ray-finned fish, amphibians, and mammals. In fish, the ancestral version of PD-L1/PD-L2 is referred to as “PD-L1.” (B) Conserved molecular interactions between PD-1 and PD-L1 (PDB accession 4ZQK): Human PD-1 residues Y68 and K78 form hydrogen bonds with PD-L1 residues F19 and D122, interactions that are conserved across species and also apply to PD-L2.

(C) Unique residues in the PD-L2 IgC domain (carbon atoms in yellow) distinguish it from PD-L1 (PDB accession 3BP5). Notably, residues N189 and S191 form an N-glycosylation site, and residue L150, together with aromatic residues at positions 166 and 174, forms a unique surface structure with currently unknown function.