title: Allele and locus-specific differences in cell surface expression and the association of HLA class I heavy chain with beta 2-microglobulin: differential effects of inhibition of glycosylation on class I subunit association.
abstract: The assembly of HLA class I antigens, and the contribution of the single N-linked glycan to this process were examined. We observed a requirement for N-linked glycosylation in the proper assembly and surface expression of HLA-B locus products in particular, although considerable variation was seen within the allelic series of the HLA-A and B loci. We conclude that the single N-linked glycan can contribute in a major way to that conformation of the heavy (H) chain which is competent to associate with the light chain beta 2-microglobulin, and that the presence, rather than the type, of carbohydrate chain is important in this respect. The association of human class I H chains with beta 2-microglobulin shows biphasic kinetics, where an initially rapid phase is followed by a prolonged period during which no further association can be measured. It appears that HLA-C H chains are initially synthesized in amounts similar to HLA-A and B H chains, but associate inefficiently with beta 2-microglobulin, resulting in low expression of HLA-C at the cell surface. The individual stages of assembly and maturation of class I antigens including the transfer from Golgi to cell surface were found to display characteristic allelic variation.
authors.affiliation: The Netherlands Cancer Institute (Antoni van Leeuwenhoek-Huis), Amsterdam.
authors.forename: J J
authors.initials: JJ
authors.lastname: Neefjes
authors.forename: H L
authors.initials: HL
authors.lastname: Ploegh
mesh_terms: D017485:1-Deoxynojirimycin; D000483:Alleles; D001692:Biological Transport; D002462:Cell Membrane / Q000378:metabolism; D005944:Glucosamine / Q000031:analogs & derivatives / Q000494:pharmacology; D006031:Glycosylation; D006680:HLA Antigens / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D011487:Protein Conformation; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D014415:Tunicamycin / Q000494:pharmacology; D001613:beta 2-Microglobulin / Q000378:metabolism*
chemical_list: D006680:HLA Antigens; D001613:beta 2-Microglobulin; D014415:Tunicamycin; D017485:1-Deoxynojirimycin; D005944:Glucosamine