Two novel routes of transporter associated with antigen processing (TAP)-independent major histocompatibility complex class I antigen processing

J Exp Med. 1997 Oct 6;186(7):1087-98. doi: 10.1084/jem.186.7.1087.


Jaw1 is an endoplasmic reticulum (ER) resident protein representative of a class of proteins post translationally inserted into membranes via a type II membrane anchor (cytosolic NH2 domain, lumenal COOH domain) in a translocon-independent manner. We found that Jaw1 can efficiently deliver a COOH-terminal antigenic peptide to class I molecules in transporter associated with antigen processing (TAP)-deficient cells or cells in which TAP is inactivated by the ICP47 protein. Peptide delivery mediated by Jaw1 to class I molecules was equal or better than that mediated by the adenovirus E3/19K glycoprotein signal sequence, and was sufficient to enable cytofluorographic detection of newly recruited thermostabile class I molecules at the surface of TAP-deficient cells. Deletion of the transmembrane region retargeted Jaw1 from the ER to the cytosol, and severely, although incompletely, abrogated its TAP-independent peptide carrier activity. Use of different protease inhibitors revealed the involvement of a nonproteasomal protease in the TAP-independent activity of cytosolic Jaw1. These findings demonstrate two novel TAP-independent routes of antigen processing; one based on highly efficient peptide liberation from the COOH terminus of membrane proteins in the ER, the other on delivery of a cytosolic protein to the ER by an unknown route.

MeSH terms

  • Antigen Presentation / immunology*
  • Blotting, Western
  • CD8-Positive T-Lymphocytes / immunology
  • Carrier Proteins / metabolism*
  • Cell Line
  • Cytosol / metabolism
  • Endopeptidases / metabolism
  • Endoplasmic Reticulum / enzymology
  • Gene Expression Regulation
  • HeLa Cells
  • Histocompatibility Antigens Class I / immunology*
  • Humans
  • Membrane Proteins / genetics
  • Membrane Proteins / immunology
  • Membrane Proteins / metabolism*
  • Microscopy, Immunoelectron
  • Peptides / metabolism
  • Protease Inhibitors / pharmacology
  • Recombinant Fusion Proteins
  • Transformation, Genetic
  • Vaccinia virus / genetics
  • Viral Proteins / genetics
  • Viral Proteins / metabolism


  • Carrier Proteins
  • Histocompatibility Antigens Class I
  • IRAG2 protein, human
  • Membrane Proteins
  • Peptides
  • Protease Inhibitors
  • Recombinant Fusion Proteins
  • Viral Proteins
  • Endopeptidases