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

Eur J Immunol. 1988 May;18(5):801-10. doi: 10.1002/eji.1830180522.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Deoxynojirimycin
  • Alleles
  • Biological Transport
  • Cell Membrane / metabolism
  • Glucosamine / analogs & derivatives
  • Glucosamine / pharmacology
  • Glycosylation
  • HLA Antigens / metabolism*
  • Humans
  • Kinetics
  • Protein Conformation
  • Protein Processing, Post-Translational / drug effects
  • Tunicamycin / pharmacology
  • beta 2-Microglobulin / metabolism*

Substances

  • HLA Antigens
  • beta 2-Microglobulin
  • Tunicamycin
  • 1-Deoxynojirimycin
  • Glucosamine