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

Curr Biol. 1998 Jan 1;8(1):1-10. doi: 10.1016/s0960-9822(98)70014-4.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Amino Acid Sequence
  • Animals
  • Antibodies, Monoclonal
  • Antiporters / metabolism*
  • Binding Sites
  • Cell Line
  • HLA Antigens / genetics
  • HLA Antigens / metabolism*
  • Histocompatibility Antigens Class I / genetics
  • Histocompatibility Antigens Class I / metabolism*
  • Humans
  • Immunoglobulins / metabolism*
  • Membrane Transport Proteins
  • Mice
  • Protein Binding
  • Protein Sorting Signals / metabolism*
  • Saguinus
  • Surface Properties
  • Tumor Necrosis Factor Receptor Superfamily, Member 7 / metabolism*

Substances

  • Antibodies, Monoclonal
  • Antiporters
  • HLA Antigens
  • HLA-E antigen
  • Histocompatibility Antigens Class I
  • Immunoglobulins
  • Membrane Transport Proteins
  • Protein Sorting Signals
  • Tumor Necrosis Factor Receptor Superfamily, Member 7
  • tapasin