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By
ík,*
From the * Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases,
Bethesda, Maryland 20892-0440; the 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.
Department of Medicine, University of Minnesota,
Minneapolis, Minnesota 55455; the § Electron Microscopy Laboratory, University of Zurich, Zurich,
Switzerland CH-8091; and the ¶ Mount Sinai School of Medicine of the City University of New
York, Department of Pharmacology, New York 10029
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