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.
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6 October 1997
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October 06 1997
Two Novel Routes of Transporter Associated with Antigen Processing (TAP)-independent Major Histocompatibility Complex Class I Antigen Processing
Heidi Link Snyder,
Heidi Link Snyder
From the *Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892-0440; the ‡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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Igor Bačík,
Igor Bačík
From the *Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892-0440; the ‡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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Jack R. Bennink,
Jack R. Bennink
From the *Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892-0440; the ‡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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Grainne Kearns,
Grainne Kearns
From the *Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892-0440; the ‡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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Timothy W. Behrens,
Timothy W. Behrens
From the *Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892-0440; the ‡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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Thomas Bächi,
Thomas Bächi
From the *Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892-0440; the ‡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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Marian Orlowski,
Marian Orlowski
From the *Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892-0440; the ‡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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Jonathan W. Yewdell
Jonathan W. Yewdell
From the *Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892-0440; the ‡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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Heidi Link Snyder
,
Igor Bačík
,
Jack R. Bennink
,
Grainne Kearns
,
Timothy W. Behrens
,
Thomas Bächi
,
Marian Orlowski
,
Jonathan W. Yewdell
From the *Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892-0440; the ‡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
Address correspondence to J.R. Bennink and J.W. Yewdell, Room 213, Building 4, NIH, Bethesda, MD 20892-0440. Phone: 301-496-7533; FAX: 301-402-7362; E-mail: [email protected], [email protected]
1
Abbreviations used in this paper: BFA, brefeldin A; ER, endoplasmic reticulum; FBS, fetal bovine serum; MOI, multiplicity of infection; NP, nucleoprotein; rVV, recombinant vaccinia virus; TAP, transporter associated with antigen processing; VV, vaccinia virus.
Received:
May 08 1997
Revision Received:
July 16 1997
Online ISSN: 1540-9538
Print ISSN: 0022-1007
1997
J Exp Med (1997) 186 (7): 1087–1098.
Article history
Received:
May 08 1997
Revision Received:
July 16 1997
Citation
Heidi Link Snyder, Igor Bačík, Jack R. Bennink, Grainne Kearns, Timothy W. Behrens, Thomas Bächi, Marian Orlowski, Jonathan W. Yewdell; Two Novel Routes of Transporter Associated with Antigen Processing (TAP)-independent Major Histocompatibility Complex Class I Antigen Processing . J Exp Med 6 October 1997; 186 (7): 1087–1098. doi: https://doi.org/10.1084/jem.186.7.1087
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