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R in Human Dendritic Cells Controls Cross-Presentation of Antigen-Antibody Complexes1
,
* Research Division, Hospital for Special Surgery,
Department of Medicine, Weill Medical College, Cornell University, and
Immunology Program, Weill Graduate School of Medical Sciences, New York, NY 10021
Receptors for IgG (Fc
R) expressed in dendritic cells (DCs) influence the initiation of Ab-mediated immunity. Dynamic variations in FcR expression allow DCs to adjust their capacity to capture Ab-opsonized Ag. The current paradigm predicts a progressive decline in FcR-mediated phagocytic function upon DC maturation. Surprisingly, we find that expression of the phagocytic receptor FcRIIa is preserved in immature and mature DCs at comparable levels with macrophages. Moreover, phagocytosis of antigenic peptides directed to FcRIIa on DCs leads to dramatic increases in Ag cross-presentation and T cell activation. In immature DCs, high expression of inhibitory FcRIIb correlates with decreased uptake and cross-presentation of Ab-Ag complexes. In contrast, engagement of FcRIIb is not associated with changes in cross-presentation in mature DCs. We provide evidence that FcRIIb expression is patently reduced in mature DCs, an effect that is modulated by treatment with cytokines. The regulated expression of activating and inhibitory FcRs in DCs emerges as a critical checkpoint in the process of Ag uptake and cross-presentation
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 grants from National Institutes of Health (NIH)/National Institute of Arthritis and Musculoskeletal and Skin Diseases (RO1 AR049765 and R21 AR050643), the Lupus Research Institute, and the Arthritis Foundation (to L.P.). This investigation was conducted in a facility constructed with support from Research Facilities Improvement Program Grant Number C06-RR12538-01 from the National Center for Research Resources, NIH.
2 Address correspondence and reprint requests to Dr. Luminita Pricop, Hospital for Special Surgery, 535 East 70th Street, New York, NY 10021. E-mail address: PricopL{at}hss.edu
3 Abbreviations used in this paper: DC, dendritic cell; Ma, macrophage; iDC, immature DC; mDC, mature DC; MP, matrix peptide; MHC-I, MHC class I; PI, phagocytic index; MFI, mean fluorescence intensity; SFC, spot-forming cell.
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