Abstract
Dendritic cells (DCs) are professional antigen-presenting cells with antigen recognition molecules on the surface. Clec9a is selectively expressed on mouse CD8a+ DCs and CD103+ DCs subsets, which are functionally similar to human BDCA3+ DCs. It is reported that Clec9a is responsible for the antigen cross-presentation of these DC subsets. In the present study, by using phage display technique, we discovered a novel peptide WH, which can selectively bind to mouse Flt3L induced Clec9a+ DCs or Clec9a over-expressed HEK-293T cells. Furthermore, by using computer-aided docking model and mutation assay, we observed that Asp248 and Trp250 are two key residues for Clec9a to bind with peptide WH. When coupled with OVA257-264 epitope, peptide WH can significantly enhance the ability of Clec9a+ DCs to activate OVA-specific CD8+ T cells, which elicit strong ability to secret IFN-γ, express perforin and granzyme B mRNA. In B16-OVA lung metastasis mouse model, WH-OVA257-264 fusion peptide can also enhance the activation of CD8+ T cells and decrease the lung metastasis loci. All these results suggested that peptide WH could be considered as an antigen delivery carrier targeting Clec9a+ DCs for cancer immunotherapy.
Highlights
Dendritic cells are the professional antigenpresenting cells (APCs) which play important roles in activation of naïve CD8+ T cell in response to foreign antigens or dead cell derived antigens [1, 2]
All these results suggested that peptide WH could be considered as an antigen delivery carrier targeting Clec9a+ Dendritic cells (DCs) for cancer immunotherapy
It was reported that the C-type lectin-like domain (CTLD) of Clec9a was important to the antigen recognition and endocytosis
Summary
Dendritic cells are the professional antigenpresenting cells (APCs) which play important roles in activation of naïve CD8+ T cell in response to foreign antigens or dead cell derived antigens [1, 2]. CD8a+ DCs (functionally similar to the BDCA3+ DCs in human) are the major subset for antigen cross-presentation which responsible for the activation of anti-tumor CD8+ T cell response [3, 4]. It raises the possibility to design anti-tumor vaccines targeting this subset of DCs. Some specific C-type lectin members expressed on CD8a+ DCs, such as Clec9a ( named as DNGR-1) [3, 5], DEC205[6, 7] and Dectin-1[8, 9], are reported to be responsible for antigen uptake. Clec9a is uniquely expressed on mouse CD8a+DC, CD103+DC and some pDC [3, 5]. Clec9a is selectively expressed on human BDCA3+ DC [10,11,12]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
