Abstract
The potential of the skin immune system to generate immune responses is well established, and the skin is actively exploited as a vaccination site. Human skin contains several antigen-presenting cell subsets with specialized functions. In particular, the capacity to cross-present exogenous antigens to CD8+ T cells is of interest for the design of effective immunotherapies against viruses or cancer. Here, we show that primary human Langerhans cells (LCs) were able to cross-present a synthetic long peptide (SLP) to CD8+T cells. In addition, modification of this SLP using antibodies against the receptor langerin, but not dectin-1, further enhanced the cross-presenting capacity of LCs through routing of internalized antigens to less proteolytic early endosome antigen 1+early endosomes. The potency of LCs to enhance CD8+T-cell responses could be further increased through activation of LCs with the toll-like receptor 3 ligand polyinosinic:polycytidylic acid (pI:C). Altogether, the data provide evidence that human LCs are able to cross-present antigens after langerin-mediated internalization. Furthermore, the potential for antigen modification to target LCs specifically provides a rationale for generating effective anti-tumor or anti-viral cytotoxic T lymphocyte responses.
Original language | English |
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Pages (from-to) | 360-370 |
Number of pages | 11 |
Journal | Cellular Immunology |
Volume | 14 |
Issue number | 4 |
DOIs | |
Publication status | Published - Apr 2017 |
Keywords
- Antibodies
- Antigens
- Antigens, CD
- Cell Compartmentation
- Cell Differentiation
- Cross-Priming
- Endocytosis
- Endosomes
- Humans
- Journal Article
- Langerhans Cells
- Lectins, C-Type
- Ligands
- Mannose-Binding Lectins
- Peptides
- Poly I-C
- Skin
- Toll-Like Receptors