Epidermal Langerhans cells rapidly capture and present antigens from C-type lectin-targeting antibodies deposited in the dermis.
Antigen-presenting cells can capture antigens that are deposited in the skin, including vaccines given subcutaneously. These include different dendritic cells (DCs) such as epidermal Langerhans cells (LCs), dermal DCs, and dermal langerin+ DCs. To evaluate access of dermal antigens to skin DCs, we used mAb to two C-type lectin endocytic receptors, DEC-205/CD205 and langerin/CD207. When applied to murine and human skin explant cultures, these mAbs were efficiently taken up by epidermal LCs. In addition, anti-DEC-205 targeted langerin+ CD103+ and langerin- CD103- mouse dermal DCs. Unexpectedly, intradermal injection of either mAb, but not isotype control, resulted in strong and rapid labeling of LCs in situ, implying that large molecules can diffuse through the basement membrane into the epidermis. Epidermal LCs targeted in vivo by ovalbumin-coupled anti-DEC-205 potently presented antigen to CD4+ and CD8+ T cells in vitro. However, to our surprise, LCs targeted through langerin were unable to trigger T-cell proliferation. Thus, epidermal LCs have a major function in uptake of lectin-binding antibodies under standard vaccination conditions.
Flacher
Vincent
V
Department of Dermatology and Venereology, Innsbruck Medical University, Innsbruck, Austria.
Tripp
Christoph H
CH
Stoitzner
Patrizia
P
Haid
Bernhard
B
Ebner
Susanne
S
Del Frari
Barbara
B
Koch
Franz
F
Park
Chae Gyu
CG
Steinman
Ralph M
RM
Idoyaga
Juliana
J
Romani
Nikolaus
N
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D017951:Antigen Presentation / Q000276:immunology*; D000954:Antigens, Surface / Q000276:immunology*; D002455:Cell Division / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D002478:Cells, Cultured; D020405:Dermis / Q000166:cytology / Q000276:immunology*; D000078404:Epidermal Cells; D004817:Epidermis / Q000276:immunology*; D006801:Humans; D007271:Injections, Intradermal; D007801:Langerhans Cells / Q000166:cytology / Q000276:immunology*; D037181:Lectins, C-Type / Q000276:immunology*; D037241:Mannose-Binding Lectins / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; C498497:Cd207 protein, mouse; D037181:Lectins, C-Type; D037241:Mannose-Binding Lectins