Cell surface expression of HLA-E: interaction with human beta2-microglobulin and allelic differences

Eur J Immunol. 1999 Feb;29(2):537-47. doi: 10.1002/(SICI)1521-4141(199902)29:02<537::AID-IMMU537>3.0.CO;2-6.


The formation of a trimeric complex composed of MHC class I heavy chain, beta2-microglobulin (beta2m) and peptide ligand is a prerequisite for its efficient transport to the cell surface. We have previously demonstrated impaired intracellular transport of the human class Ib molecule HLA-E in mouse myeloma X63 cells cotransfected with the genes for HLA-E and human beta2m (hbeta2m), which is most likely attributable to inefficient intracellular peptide loading of the HLA-E molecule. Here we demonstrate that cell surface expression of HLA-E in mouse cells strictly depends on the coexpression of hbeta2m and that soluble empty complexes of HLA-E and hbeta2m display a low degree of thermostability. Both observations imply that low affinity interaction of HLA-E with beta2m accounts to a considerable extent for the observed low degree of peptide uptake in the endoplasmic reticulum. Moreover, we show that the only allelic variation present in the caucasoid population located at amino acid position 107 (Gly or Arg) greatly affects intracellular transport and cell surface expression upon transfection of the respective alleles into mouse cells. No obvious difference was found with regard to the sequence of the peptide ligand.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Animals
  • Antigen Presentation / genetics
  • Antigen Presentation / immunology*
  • Gene Expression Regulation / immunology
  • HLA Antigens / genetics
  • HLA Antigens / immunology*
  • Histocompatibility Antigens Class I / genetics
  • Histocompatibility Antigens Class I / immunology*
  • Humans
  • Mice
  • Multiple Myeloma / genetics
  • Multiple Myeloma / immunology
  • Transfection
  • Tumor Cells, Cultured
  • beta 2-Microglobulin / genetics
  • beta 2-Microglobulin / immunology*


  • HLA Antigens
  • HLA-E antigen
  • Histocompatibility Antigens Class I
  • beta 2-Microglobulin