TAP- and tapasin-dependent HLA-E surface expression correlates with the binding of an MHC class I leader peptide.

Journal article

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.

Conclusion: 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.

Authors: Braud, V; Allan, D; Wilson, D; Mcmichael, A

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Elsevier
• Journal: Current biology : CB
• Volume: 8
• Issue: 1
• Pages: 1-10
• Publication date: 1998-01-01
• DOI: 10.1016/s0960-9822(98)70014-4
• EISSN: 1879-0445
• ISSN: 0960-9822
• Language: English
• Keywords: Histocompatibility Antigens Class I; Saguinus; Amino Acid Sequence; Humans; Antiporters; Immunoglobulins; Antibodies, Monoclonal; Mice; Binding Sites; Animals; Cell Line; Antigens, CD27; Membrane Transport Proteins; HLA Antigens; Alleles; Protein Binding; Protein Sorting Signals; Surface Properties