Monoclonal antibody (mAb)-based blockade of programmed cell death 1 (PD-1) or 
its ligand to enable antitumor T-cell immunity has been successful in treating 
multiple tumors. However, the structural basis of the binding mechanisms of the 
mAbs and PD-1 and the effects of glycosylation of PD-1 on mAb interaction are 
not well understood. Here, we report the complex structure of PD-1 with 
toripalimab, a mAb that is approved by China National Medical Products 
Administration as a second-line treatment for melanoma and is under multiple 
Phase 1-Phase 3 clinical trials in both China and the US. Our analysis reveals 
that toripalimab mainly binds to the FG loop of PD-1 with an unconventionally 
long complementarity-determining region 3 loop of the heavy chain, which is 
distinct from the known binding epitopes of anti-PD-1 mAbs with structural 
evidences. The glycan modifications of PD-1 could be observed in three potential 
N-linked glycosylation sites, while no substantial influences were detected to 
the binding of toripalimab. These findings benefit our understanding of the 
binding mechanisms of toripalimab to PD-1 and shed light for future development 
of biologics targeting PD-1. Atomic coordinates have been deposited in the 
Protein Data Bank under accession code 6JBT.