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Presentation of Exogenous Protein Antigens on Major Histocompatability Complex Class I Molecules by Dendritic Cells: Pathway of Presentation and Regulation by Cytokines
Peter Brossart and
Michael J. Bevan
From the Howard Hughes Medical Institute, Department of Immunology, University of Washington, Seattle, WA.
Several recent studies have shown that dendritic cells (DC) pulsed with soluble proteins can present peptide epitopes derived from these exogenous antigens on major histocompatability complex (MHC) class I molecules and induce an antigen-specific cytotoxic T lymphocyte (CTL) response. We provide evidence here that DC use macropinocytosis to capture soluble antigens that are then presented on MHC class I molecules. The presentation of an epitope derived from soluble ovalbumin was transporter associated with antigen presentation (TAP)-dependent, brefeldin A-sensitive, blocked by inhibitors of proteasomes, and resistant to chloroquine. These data suggest that exogenous antigens access the cytosol of DC and are proccessed for presentation via the same pathway described for conventional MHC class I-restricted cytosolic antigens. Proinflammatory mediators such as tumor necrosis factor- (TNF-) and lipopolysaccharide (LPS) reduced the efficiency of ovalbumin presentation via this pathway. This reduced presentation was not due to impaired expression of class I molecules because these substances upregulated the cell surface expression of Kb-molecules comparable to levels induced by interferon- (IFN-) treatment. The addition of IFN- increased ovalbumin presentation even in the presence of TNF- or LPS. These results show that DC might be involved in the cross-priming phenomenon. This could offer the immune system an additional pathway for effective priming of cytotoxic T cells and provide the possibility to activate both CD4 and CD8 T-cell responses.
Blood, Vol. 90 No. 4 (August 15), 1997:
pp. 1594-1599
© 1997 by The American Society of Hematology.
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P. Brossart, A. Zobywalski, F. Grünebach, L. Behnke, G. Stuhler, V. L. Reichardt, L. Kanz, and W. Brugger
Tumor Necrosis Factor {{alpha}} and CD40 Ligand Antagonize the Inhibitory Effects of Interleukin 10 on T-Cell Stimulatory Capacity of Dendritic Cells
Cancer Res.,
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60(16):
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[Abstract]
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S. Aiello, M. Noris, G. Piccinini, S. Tomasoni, F. Casiraghi, S. Bonazzola, M. Mister, M. H. Sayegh, and G. Remuzzi
Thymic Dendritic Cells Express Inducible Nitric Oxide Synthase and Generate Nitric Oxide in Response to Self- and Alloantigens
J. Immunol.,
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M. K. Song, S. W. Lee, Y. S. Suh, K. J. Lee, and Y. C. Sung
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J. Virol.,
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[Abstract]
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R. M. Vabulas, H. Pircher, G. B. Lipford, H. Hacker, and H. Wagner
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J. Immunol.,
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S. Riegler, H. Hebart, H. Einsele, P. Brossart, G. Jahn, and C. Sinzger
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P. Brossart, K. S. Heinrich, G. Stuhler, L. Behnke, V. L. Reichardt, S. Stevanovic, A. Muhm, H.-G. Rammensee, L. Kanz, and W. Brugger
Identification of HLA-A2-Restricted T-Cell Epitopes Derived From the MUC1 Tumor Antigen for Broadly Applicable Vaccine Therapies
Blood,
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[Abstract]
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S. Muerkoster, M. Rocha, P. R. Crocker, V. Schirrmacher, and V. Umansky
Sialoadhesin-Positive Host Macrophages Play an Essential Role in Graft-Versus-Leukemia Reactivity in Mice
Blood,
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[Abstract]
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R. N. L. Motte, A. H. Sharpe, J. A. Bluestone, and M. B. Mokyr
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P. Guermonprez, D. Ladant, G. Karimova, A. Ullmann, and C. Leclerc
Direct Delivery of the Bordetella pertussis Adenylate Cyclase Toxin to the MHC Class I Antigen Presentation Pathway
J. Immunol.,
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J. Wassenberg, C Dezfulian, and C. Nicchitta
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I. V. Redchenko and A. B. Rickinson
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J. Virol.,
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P. Brossart, F. Grunebach, G. Stuhler, V. L. Reichardt, R. Mohle, L. Kanz, and W. Brugger
Generation of Functional Human Dendritic Cells From Adherent Peripheral Blood Monocytes by CD40 Ligation in the Absence of Granulocyte-Macrophage Colony-Stimulating Factor
Blood,
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[Abstract]
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