biostudies-literatureHoek MDutch Research Council (NWO)4518-4528https://www.ebi.ac.uk/biostudies/studies/S-EPMC8419865biostudies-literatureUnknown20(9)Presentation of antigens by human leukocyte antigen (HLA) complexes at the cell surface is a key process in the immune response. The α-chain, containing the peptide-binding groove, is one of the most polymorphic proteins in the proteome. All HLA class I α-chains carry a conserved N-glycosylation site, but little is known about its nature and function. Here, we report an in-depth characterization of N-glycosylation features of HLA class I molecules. We observe that different HLA-A α-chains carry similar glycosylation, distinctly different from the HLA-B, HLA-C, and HLA-F α-chains. Although HLA-A displays the broadest variety of glycan characteristics, HLA-B α-chains carry mostly mature glycans, and HLA-C and HLA-F α-chains carry predominantly high-mannose glycans. We expected these glycosylJournal of proteome researchAllotype-Specific Glycosylation and Cellular Localization of Human Leukocyte Antigen Class I Proteins.PMC8419865ICI00003184.034.019Hoek MHeck AJRWu WDemmers LCfalseAllotype-Specific Glycosylation and Cellular Localization of Human Leukocyte Antigen Class I Proteins.Presentation of antigens by human leukocyte antigen (HLA) complexes at the cell surface is a key process in the immune response. The α-chain, containing the peptide-binding groove, is one of the most polymorphic proteins in the proteome. All HLA class I α-chains carry a conserved N-glycosylation site, but little is known about its nature and function. Here, we report an in-depth characterization of N-glycosylation features of HLA class I molecules. We observe that different HLA-A α-chains carry similar glycosylation, distinctly different from the HLA-B, HLA-C, and HLA-F α-chains. Although HLA-A displays the broadest variety of glycan characteristics, HLA-B α-chains carry mostly mature glycans, and HLA-C and HLA-F α-chains carry predominantly high-mannose glycans. We expected these glycosyl2021-01-01T00:00:00Z2021 Sep2026-05-08T19:16:32.57Z2022-02-11T10:21:14.56ZS-EPMC84198653441576210.1021/acs.jproteome.1c00466