TAP- and tapasin-dependent HLA-E surface expression correlates with the binding of an MHC class I leader peptide.
BACKGROUND
The human major histocompatibility complex (MHC) class lb molecule HLA-E is transcribed in most tissues but little is known about its localisation within the cell. We have recently shown that HLA-E binds signal-sequence-derived peptides from human MHC class I molecules in vitro.


RESULTS
Using a newly characterised antibody recognising HLA-E, we show that HLA-E is expressed at the cell surface. We demonstrate that HLA-E surface expression is correlated with the presence of MHC class I molecules which provide suitable leader sequence peptides capable of binding to HLA-E. Further studies on the interaction of HLA-E with molecules in the endoplasmic reticulum revealed that HLA-E associates with the transporter associated with antigen processing (TAP) and calreticulin, and that HLA-E expression is TAP-dependent and tapasin-dependent. In addition, HLA-E dissociates from TAP upon binding of MHC class I leader sequence peptides.


CONCLUSIONS
These experiments establish that surface expression of HLA-E is regulated by the binding of a restricted pool of peptides from the leader sequence of MHC class I molecules. The correlation between HLA-E and MHC class I surface expression might be relevant to the function of HLA-E. Our results also show that, although these HLA-E binding peptides are derived from signal sequences, they may be released back into the cytosol and subsequently translocated by the TAP complex and loaded onto HLA-E molecules.
Braud
V M
VM
Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, OX3 9DS, UK. vbraud@worf.molbiol.ox.ac.uk
Allan
D S
DS
Wilson
D
D
McMichael
A J
AJ
D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal; D017920:Antiporters / Q000378:metabolism*; D001665:Binding Sites; D002460:Cell Line; D006680:HLA Antigens / Q000235:genetics / Q000378:metabolism*; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007136:Immunoglobulins / Q000378:metabolism*; D026901:Membrane Transport Proteins; D051379:Mice; D011485:Protein Binding; D021382:Protein Sorting Signals / Q000378:metabolism*; D012452:Saguinus; D013499:Surface Properties; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000378:metabolism*; D000097625:HLA-E Antigens
D000911:Antibodies, Monoclonal; D017920:Antiporters; D006680:HLA Antigens; D015395:Histocompatibility Antigens Class I; D007136:Immunoglobulins; D026901:Membrane Transport Proteins; D021382:Protein Sorting Signals; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D000097625:HLA-E Antigens; C107762:tapasin