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This Article Full Text Full Text (PDF) All Versions of this Article: jimmunol.0901828v1 183/7/4205    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Related articles in The JI Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Google Scholar Articles by Lev, A. Articles by Yewdell, J. W. PubMed PubMed Citation Articles by Lev, A. Articles by Yewdell, J. W.

Efficient Cross-Priming of Antiviral CD8⁺ T Cells by Antigen Donor Cells Is GRP94 Independent¹

Avital Lev^*, Peniel Dimberu^*, Suman R. Das^*, Jason C. Maynard, Christopher V. Nicchitta, Jack R. Bennink^* and Jonathan W. Yewdell^2,*

^* Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892; and Department of Cell Biology, Duke University Medical Center, Durham, NC 27710

Cross-priming, the activation of naive CD8⁺ T cells by dendritic cells presenting Ags synthesized by other cells, is believed to play an important role in the generation of antiviral and antitumor responses. The molecular mechanism(s) underlying cross-priming remain poorly defined and highly controversial. GRP94 (gp96), an abundant endoplasmic reticulum chaperone with innate immune-activating capacity, has been widely reported to play a major role in cross-priming. In this study, we show that cells whose expression of GRP94 is silenced via transient or stable transfection with GRP94-directed small interfering RNAs demonstrate no reduction in their abilities to generate class I peptide complexes in cultured cells or to prime antiviral CD8⁺ T cell responses in vivo. In demonstrating the dispensability of GRP94, our finding points to the importance of alternative mechanisms for generation of class I peptide complexes from endogenous and exogenous Ags and immunogens.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ J.R.B. and J.W.Y. are supported by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases. C.V.N. is supported by Grant CA104392 from the National Institutes of Health.

² Address correspondence and reprint requests to Dr. Jonathan W. Yewdell, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Building 33, Bethesda, MD 20892. E-mail address: jyewdell{at}nih.gov

³ Abbreviations used in this paper: DC, dendritic cell; ER, endoplasmic reticulum; GRP94, glucose-regulated protein 94; IAV, influenza A virus; neo, aminoglycoside phosphotransferase; NP, nucleoprotein, VV, vaccinia virus; VSV, vesicular stomatitis virus; siRNA, small interfering RNA; PEC, peritoneal exudate cell; shRNA, short hairpin RNA.

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The JI 2009 183: 4143-4144. [Full Text]