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An essential function of tapasin in quality control of HLA-G molecules.

Tapasin plays an important role in the quality control of major histocompatibility complex (MHC) class I assembly, but its precise function in this process remains controversial. Whether tapasin participates in the assembly of HLA-G has not been studied. HLA-G, an MHC class Ib molecule that binds a more restricted set of peptides than class Ia molecules, is a particularly interesting molecule, because during assembly, it recycles between the endoplasmic reticulum (ER) and the cis-Golgi until it is loaded with a high affinity peptide. We have taken advantage of this unusual trafficking property of HLA-G and its requirement for high affinity peptides to demonstrate that a critical function of tapasin is to transform class I molecules into a high affinity, peptide-receptive form. In the absence of tapasin, HLA-G molecules cannot bind high affinity peptides, and an abundant supply of peptides cannot overcome the tapasin requirement for high affinity peptide loading. The addition of tapasin renders HLA-G molecules capable of loading high affinity peptides and of transporting to the surface, suggesting that tapasin is a prerequisite for the binding of high-affinity ligands. Interestingly, the "tapasin-dependent" HLA-G molecules are not empty in the absence of tapasin but are in fact associated with suboptimal peptides and continue to recycle between the ER and the cis-Golgi. Together with the finding that empty HLA-G heterodimers are strictly retained in the ER and degraded, our data suggest that MHC class I molecules bind any available peptides to avoid ER-mediated degradation and that the peptides are in turn replaced by higher affinity peptides with the aid of tapasin.

Pubmed ID: 12582157

Authors

  • Park B
  • Ahn K

Journal

The Journal of biological chemistry

Publication Data

April 18, 2003

Associated Grants

None

Mesh Terms

  • 3T3 Cells
  • Animals
  • Antigens
  • Antiporters
  • Blotting, Western
  • Cell Membrane
  • Dimerization
  • Dose-Response Relationship, Drug
  • Endoplasmic Reticulum
  • Flow Cytometry
  • Golgi Apparatus
  • HLA Antigens
  • HLA-G Antigens
  • Histocompatibility Antigens Class I
  • Humans
  • Immunoglobulins
  • Kinetics
  • Ligands
  • Membrane Transport Proteins
  • Mice
  • Microscopy, Fluorescence
  • Microsomes
  • Peptides
  • Precipitin Tests
  • Protein Conformation
  • Temperature