Langerhans cells cross-present antigen derived from skin

doi:10.1073/pnas.0509307103

Langerhans cells cross-present antigen derived from skin

Departments of *Dermatology and
^‡Biochemical Pharmacology, Innsbruck Medical University, 6020 Innsbruck, Austria;
^†Malaghan Institute of Medical Research, Wellington 6005, New Zealand; and
^§Center for Immunology, Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55455

Edited by Ralph M. Steinman, The Rockefeller University, New York, NY, and approved March 28, 2006 (received for review October 25, 2005)

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 antigen-specific 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, like cytokine production and cytotoxicity, and may thereby critically contribute in epicutaneous vaccination approaches.

Footnotes

^¶To whom correspondence should be addressed. E-mail: nikolaus.romani{at}uibk.ac.at
Author contributions: P.S., F.R., and N.R. designed research; P.S., C.H.T., A.E., K.M.P., J.Y.J., and L.B. performed research; L.B. contributed K14 mOVA transgenic mice; P.S. and N.R. analyzed data; and P.S. and N.R. wrote the paper.
Conflict of interest statement: No conflicts declared.
This paper was submitted directly (Track II) to the PNAS office.
Abbreviations:

Abbreviations:

DC,

dendritic cell;

LC,

Langerhans cell;

OVA,

ovalbumin.