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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Harris, Nicola Geuking, Markus Schrempf, Sabrina Eschli, Bruno Zellweger, Raphael Freigang, Stefan Zinkernagel, Rolf M. Hengartner, Hans Quirin, Katharina Weber, Jacqueline |
| Description | Author Affiliation: Freigang S ( Institute of Experimental Immunology, Department of Pathology, University Hospital, Schmelzbergstrasse 12, CH-8091 Zurich, Switzerland. stefan.freigang@gmx.net); |
| Abstract | Recent studies indicate that T cell cross-priming preferentially occurs against long-lived, stable proteins. We have studied cross-priming by using the glycoprotein (GP) of lymphocytic choriomeningitis virus (LCMV), a protein that normally is not MHC class I cross-presented. This study shows that a C-terminally truncated, noncleavable variant of LCMV-GP led to the accumulation of stable, soluble GP trimers in the endoplasmic reticulum (ER) of the antigen donor cell, and thereby converted LCMV-GP into a potent immunogen for cytotoxic T lymphocyte cross-priming. Immunization of mice with tumor cells expressing an ER-retained LCMV-GP variant cross-primed protective antiviral cytotoxic T lymphocyte responses in vivo at least 10,000-fold better than immunization with cells expressing the cross-presentation-'resistant' wild-type LCMV-GP. Thus the ER is a cellular compartment that can provide antigen for cross-presentation, and modifications affecting stability and subcellular localization of the antigen significantly increase its availability for MHC class I cross-presentation. These findings impinge on vaccine strategies. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 33 |
| Volume Number | 104 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2007-08-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | CD8-Positive T-Lymphocytes Immunology Endoplasmic Reticulum Metabolism Glycoproteins Lymphocytic Choriomeningitis Virus Viral Proteins Animals Blotting, Western Flow Cytometry HeLa Cells Mice Mice, Inbred BALB C Mice, Transgenic Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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