Langerin-mediated internalization of a modified peptide routes antigens to early endosomes and enhances cross-presentation by human Langerhans cells.
Cell Mol Immunol
; 14(4): 360-370, 2017 Apr.
Article
in En
| MEDLINE
| ID: mdl-26456691
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 polyinosinicpolycytidylic acid (pIC). 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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Peptides
/
Endosomes
/
Antigens, CD
/
Langerhans Cells
/
Lectins, C-Type
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Mannose-Binding Lectins
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Cross-Priming
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Endocytosis
/
Antigens
Limits:
Humans
Language:
En
Journal:
Cell Mol Immunol
Journal subject:
ALERGIA E IMUNOLOGIA
Year:
2017
Type:
Article
Affiliation country:
Netherlands