[ASAP] Allotype-Specific Glycosylation and Cellular Localization of Human Leukocyte Antigen Class I Proteins

3 years ago

[ASAP] Allotype-Specific Glycosylation and Cellular Localization of Human Leukocyte Antigen Class I Proteins

Max Hoek, Laura C. Demmers, Wei Wu, Albert J. R. Heck

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 glycosylation features to be directly linked to cellular localization of the HLA complexes. Indeed, analyzing HLA class I complexes from crude plasma and inner membrane-enriched fractions confirmed that most HLA-B complexes can be found at the plasma membrane, while most HLA-C and HLA-F molecules reside in the endoplasmic reticulum and Golgi membrane, and HLA-A molecules are more equally distributed over these cellular compartments. This allotype-specific cellular distribution of HLA molecules should be taken into account when analyzing peptide antigen presentation by immunopeptidomics. This article has not yet been cited by other publications.

Publisher URL: http://feedproxy.google.com/~r/acs/jprobs/~3/7tODSr_8b3E/acs.jproteome.1c00466

Open URL: https://pubs.acs.org/doi/pdf/10.1021/acs.jproteome.1c00466

DOI: 10.1021/acs.jproteome.1c00466