{"database":"ENA","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Fastqsanger.gz":["ftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR125/052/SRR12560152/SRR12560152_1.fastq.gz","ftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR125/051/SRR12560151/SRR12560151_2.fastq.gz","ftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR125/051/SRR12560151/SRR12560151_1.fastq.gz","ftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR125/052/SRR12560152/SRR12560152_2.fastq.gz"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Genomics"],"center_name":["Shanghai Jiao Tong University"],"full_dataset_link":["https://www.ebi.ac.uk/ena/browser/view/PRJNA660543"],"long_description":["PD-1 plays an important role as immune checkpoint. Sintilimab is a newly approved PD-1 antibody for cancer immunotherapy with unknown binding epitope on PD-1. To elucidate the molecular mechanism for blockade of PD-1 activation by Sintilimab, in this study, we applied Antibody binding epitope Mapping (AbMap) to identify the binding epitope of Sintilimab. An epitope was successfully identified, i.e., SLAPKA, aa127-132. By constructing a serial of point mutations, the dominant residues S127, L128, A129, P130 and A132 of PD-1 were further validated by western blotting, Biolayer Interferometry (BLI), and flow cytometry. Structure analysis showed that the epitope is partially within the binding interface of PD-1 and PD-L1, and this epitope is also partially overlapped with that of Nivolumab and Pembrolizumab. These results demonstrate that Sintilimab can attenuate PD-1 activation by directly competing the interaction between PD-1 and PD-L1 through binding key residues of FG loop on PD-1. This study also proves the high efficiency and accuracy of AbMap for determining the binding epitope of therapeutic antibodies."],"repository":["ENA"],"description_synonyms":["Antigenic Determinants, Ly101, Epitope, SLEB2, antigenic determinant, ligand, hPD-1., Specificity, l17, Antigenic, 60S ribosomal protein L23, rpl23, Antigenic Specificity, CD279, IBI-308, hPD-l, Determinant, RPL23, epitope function, Pdc1, rpl17a, pd-1, hSLE1, rpl17, IBI 308, L17, Determinants, epitope role, PD1, PD-1, IBI308, Antigenic Determinant"],"additional_accession":[]},"is_claimable":false,"name":"","description":"The binding epitope of Sintilimab on PD-1 revealed by AbMap","dates":{"last_updated":"2023-05-19","first_public":"2020-09-02"},"accession":"PRJNA660543","cross_references":{}}