Cell surface expression of HLA-E: interaction with human beta(2)-microglobulin and allelic differences

The formation of a trimeric complex composed of MHC class I heavy chain, be ta 2-microglobulin (beta 2m) and peptide ligand is a prerequisite for its e fficient transport to the cell surface. We have previously demonstrated imp aired intracellular transport of the human class Ib molecule HLA-E in mouse myeloma X63 cells cotransfected with the genes for HLA-E and human beta 2m (h beta 2m), which is most likely attributable to inefficient intracellula r peptide loading of the HLA-E molecule. Here we demonstrate that cell surf ace expression of HLA-E in mouse cells strictly depends on the coexpression of h beta 2m and that soluble empty complexes of HLA-E and h beta 2m displ ay a low degree of thermostability. Both observations imply that low affini ty interaction of HLA-E with beta 2m accounts to a considerable extent for the observed low degree of peptide uptake in the endoplasmic reticulum. Mor eover, we show that the only allelic variation present in the caucasoid pop ulation located at amino acid position 107 (Gly or Arg) greatly affects int racellular transport and cell surface expression upon transfection of the r espective alleles into mouse cells. No obvious difference was found with re gard to the sequence of the peptide ligand.