PD-L1 Glycosylation and Its Impact on Binding to Clinical Antibodies.
PD-L1 Glycosylation and Its Impact on Binding to Clinical Antibodies.
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DOI：
10.1021/acs.jproteome.0c00521
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发表时间：
2021-01-01
影响因子：
4.4
通讯作者：
Goldman R
中科院分区：
文献类型：
--
作者：
Benicky J;Sanda M;Brnakova Kennedy Z;Grant OC;Woods RJ;Zwart A;Goldman R
Immune checkpoint inhibitors, including PD-L1/PD-1, are key regulators of immune response and promising targets in cancer immunotherapy. N-glycosylation of PD-L1 affects its interaction with PD-1 but little is known about the distribution of glycoforms at its four NXS/T sequons. We optimized LC-MS/MS methods using collision energy modulation for the site-specific resolution of specific glycan motifs. We demonstrate that PD-L1 on the surface of breast cancer cells carries mostly complex glycans with high proportion of polyLacNAc structures at the N219 sequon. Contrary to the full-length protein, the secreted form of PD-L1 expressed in breast MDA-MB-231 or HEK293 cells demonstrated minimum N219 occupancy and low contribution of the polyLacNAc structures. Molecular modeling of PD-L1/PD-1 interaction with N-glycans suggests that glycans at the N219 site of PD-L1 and N74 and N116 of PD-1 are involved in glycan-glycan interactions, but the impact of this potential interaction on the protein function remains at this point unknown. In addition, the interaction of PD-L1 with clinical antibodies is also affected by glycosylation. In conclusion, PD-L1 expressed in the MDA-MB-231 breast cancer cells carries polyLacNAc glycans mostly at the N219 sequon which displays the highest variability in occupancy and is most likely to influence the interaction with PD-1.
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