TI  - <prot>TAP</prot>- and <prot>tapasin</prot>-dependent <prot>HLA-E</prot> surface expression correlates with the
      binding of an MHC class I leader peptide.
PG  - 1-10
AB  - BACKGROUND: The human major histocompatibility complex (MHC) class lb
      molecule <prot>HLA-E</prot> is transcribed in most tissues but little is known about
      its localisation within the cell. We have recently shown that  <prot>HLA-E</prot>  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 <prot>HLA-E</prot> is expressed at the cell surface. We demonstrate that
      <prot>HLA-E</prot> surface expression is correlated with the presence of  MHC class I 
      molecules which provide suitable leader sequence peptides capable of
      binding to  <prot>HLA-E</prot> .  Further studies on the interaction of <prot>HLA-E</prot> with
      molecules in the endoplasmic reticulum revealed that   <prot>HLA-E</prot>   associates with
      the transporter associated with antigen processing ( <prot>TAP</prot> ) and  calreticulin ,
      and that <prot>HLA-E</prot> expression is <prot>TAP</prot>-dependent and tapasin-dependent. In
      addition,  <prot>HLA-E</prot>  dissociates from <prot>TAP</prot> upon binding of  MHC class I  leader
      sequence peptides. CONCLUSION: These experiments establish that surface
      expression of <prot>HLA-E</prot> is regulated by the binding of a restricted pool of
      peptides from the leader sequence of MHC class I molecules. The
      correlation between <prot>HLA-E</prot> and MHC class I surface expression might be
      relevant to the function of <prot>HLA-E</prot>. Our results also show that, although
      these <prot>HLA-E</prot> binding peptides are derived from signal sequences, they may
      be released back into the cytosol and subsequently translocated by the <prot>TAP</prot>
      complex and loaded onto <prot>HLA-E</prot> molecules.
AD  - Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, OX3 9DS,
