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Dendritic Cells Cross-Dressed with Peptide MHC Class I Complexes Prime CD8⁺ T Cells¹

Department of Biological Sciences, University of Maryland Baltimore County, Baltimore, MD 21250

The activation of naive CD8⁺ T cells has been attributed to two mechanisms: cross-priming and direct priming. Cross-priming and direct priming differ in the source of Ag and in the cell that presents the Ag to the responding CD8⁺ T cells. In cross-priming, exogenous Ag is acquired by professional APCs, such as dendritic cells (DC), which process the Ag into peptides that are subsequently presented. In direct priming, the APCs, which may or may not be DC, synthesize and process the Ag and present it themselves to CD8⁺ T cells. In this study, we demonstrate that naive CD8⁺ T cells are activated by a third mechanism, called cross-dressing. In cross-dressing, DC directly acquire MHC class I-peptide complexes from dead, but not live, donor cells by a cell contact-mediated mechanism, and present the intact complexes to naive CD8⁺ T cells. Such DC are cross-dressed because they are wearing peptide-MHC complexes generated by other cells. CD8⁺ T cells activated by cross-dressing are restricted to the MHC class I genotype of the donor cells and are specific for peptides generated by the donor cells. In vivo studies demonstrate that optimal priming of CD8⁺ T cells requires both cross-priming and cross-dressing. Thus, cross-dressing may be an important mechanism by which DC prime naive CD8⁺ T cells and may explain how CD8⁺ T cells are primed to Ags that are inefficiently cross-presented.

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 This work was supported by National Institutes of Health Grants CA52527, CA84232, and CA115880, Department of Defense Grant DAMD-17-01-1-0312, and Susan G. Komen Foundation Grant BCTR0503885. B.P.D. is supported by Department of Defense Grant DAMD-17-03-1-0334 predoctoral fellowship, and K.D.G. is supported by a National Institutes of Health MARC-U-STAR training grant (GM08663).

² Address correspondence and reprint requests to Dr. Suzanne Ostrand-Rosenberg, Department of Biological Sciences, University of Maryland, 1000 Hilltop Circle, Baltimore, MD 21250.

³ Abbreviations used in this paper: DC, dendritic cell; BMDC, bone marrow-derived DC; DTR, diphtheria toxin receptor; DTx, diphtheria toxin.

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