The pathway for processing leader-derived peptides that regulate the maturation and expression of Qa-1b

Immunity. 1998 Sep;9(3):413-21. doi: 10.1016/s1074-7613(00)80624-x.

Abstract

Qa-1b and its human homolog, HLA-E, predominantly bind leader peptides derived from other class I molecules. Their presentation is TAP-dependent and proteasome-independent. We demonstrate that Dd targeted to the cytosol does not generate the Qa-1b peptide epitope even in the presence of lactacystin. Cells expressing herpes virus ICP-47 block the generation of this epitope, demonstrating that TAP functions in the transport of the peptide from cytosol to ER. This reveals a pathway for antigen presentation of leader peptides that involves translocation of a protein to the ER where its leader is cleaved followed by its release into the cytosol and transport back into the ER. Further, it ensures that Qa-1b expression mirrors the normal expression of class Ia molecules.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acetylcysteine / analogs & derivatives
  • Acetylcysteine / pharmacology
  • Amino Acid Sequence
  • Animals
  • Antigen Presentation / physiology*
  • Carrier Proteins / physiology
  • Cell Membrane / metabolism
  • Cysteine Proteinase Inhibitors / pharmacology
  • Epitopes / immunology
  • Histocompatibility Antigens Class I / biosynthesis*
  • Histocompatibility Antigens Class I / genetics
  • Histocompatibility Antigens Class I / metabolism
  • Humans
  • Mice
  • Molecular Sequence Data
  • Mutation
  • Protein Sorting Signals / physiology*
  • T-Lymphocytes, Cytotoxic / drug effects
  • T-Lymphocytes, Cytotoxic / immunology
  • Transfection
  • Tumor Cells, Cultured / ultrastructure

Substances

  • Carrier Proteins
  • Cysteine Proteinase Inhibitors
  • Epitopes
  • Histocompatibility Antigens Class I
  • Protein Sorting Signals
  • Q surface antigens
  • lactacystin
  • Acetylcysteine