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Langerhans Cells Cross-Present Antigen Derived from Skin

Patrizia Stoitzner, Christoph H. Tripp, Andreas Eberhart, Kylie M. Price, Jae Y. Jung, Laura Bursch, Franca Ronchese and Nikolaus Romani
Proceedings of the National Academy of Sciences of the United States of America
Vol. 103, No. 20 (May 16, 2006), pp. 7783-7788
Stable URL: http://www.jstor.org/stable/30049334
Page Count: 6
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Langerhans Cells Cross-Present Antigen Derived from Skin
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Abstract

Dendritic cells (DC) efficiently cross-present exogenous antigen on MHC class I molecules to CD8⁺ T cells. However, little is known about cross-presentation by Langerhans cells (LC), the DCs of the epidermis. Therefore, we investigated this issue in detail. Isolated murine LCs were able to cross-present soluble ovalbumin protein on MHC-class I molecules to antigen-specific CD8⁺ T cells, albeit less potently than the CD8⁺ DC subsets from spleen. Furthermore, LCs cross-presented cell-associated ovalbumin peptide and protein expressed by neighboring keratinocytes. Use of transporter associated with antigen processing (TAP-1)-deficient mice suggested a TAP-dependent pathway. Similar observations were made with migratory LC. Antigen expressed in the epidermis was ingested by LCs during migration from the epidermis and presented to antigenspecific T cells in vitro. Cross-presentation of ovalbumin protein by LCs induced IFN-γ production and cytotoxicity in antigen-specific CD8⁺ T cells. Additionally, epicutaneous application of ovalbumin protein induced in vivo proliferation of OT-I T cells in the draining lymph nodes; this was markedly enhanced when antigen was applied to inflamed, barrier-disrupted skin. Thus, LCs cross-present exogenous antigen to CD8⁺ T cells and induce effector functions, ike cytokine production and cytotoxicity, and may thereby critically contribute in epicutaneous vaccination approaches.

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