PD-1 is a highly glycosylated inhibitory receptor expressed mainly on T cells. 
Targeting of PD-1 with monoclonal antibodies (MAbs) to block the interaction 
with its ligand PD-L1 has been successful for the treatment of multiple tumors. 
However, polymorphisms at N-glycosylation sites of PD-1 exist in the human 
population that might affect antibody binding, and dysregulated glycosylation 
has been observed in the tumor microenvironment. Here, we demonstrate varied 
N-glycan composition in PD-1, and show that the binding affinity of 
camrelizumab, a recently approved PD-1-specific MAb, to non-glycosylated PD-1 
proteins from E. coli is substantially decreased compared with glycosylated 
PD-1. The structure of the camrelizumab/PD-1 complex reveals that camrelizumab 
mainly utilizes its heavy chain to bind to PD-1, while the light chain 
sterically inhibits the binding of PD-L1 to PD-1. Glycosylation of asparagine 58 
(N58) promotes the interaction with camrelizumab, while the efficiency of 
camrelizumab to inhibit the binding of PD-L1 is substantially reduced for 
glycosylation-deficient PD-1. These results increase our understanding of how 
glycosylation affects the activity of PD-1-specific MAbs during immune 
checkpoint therapy.