Cutting Edge: Langerin/CD207 Receptor on Dendritic Cells Mediates Efficient Antigen Presentation on MHC I and II Products In Vivo

Abstract

The targeted delivery of Ags to dendritic cell (DCs) in vivo greatly improves the efficiency of Ag presentation to T cells and allows an analysis of receptor function. To evaluate the function of Langerin/CD207, a receptor expressed by subsets of DCs that frequently coexpress the DEC205/CD205 receptor, we genetically introduced OVA into the C terminus of anti-receptor Ab H chains. Taking advantage of the new L31 mAb to the extracellular domain of mouse Langerin, we find that the hybrid Ab targets appropriate DC subsets in draining lymph nodes and spleen. OVA is then presented efficiently to CD8+ and CD4+ T cells in vivo, which undergo 4–8 cycles of division in 3 days. Peptide MHC I and II complexes persist for days. Dose response studies indicate only modest differences between Langerin and DEC receptors in these functions. Thus, Langerin effectively mediates Ag presentation.

Targeting of macrophage galactose‐type C‐type lectin (MGL) induces DC signaling and activation

“…In other studies, C-type lectin activation resulted in the secretion of multiple cytokines and chemokines by DCs [32,34,35], even if the upregulation of costimulatory molecules was not always detected. Moreover, C-type lectin targeting increased DC cross-presentation or improved the activation by DCs of specific lymphocyte subsets [36,37].In our system the engagement of MGL by both ligands induced activation of antigen-specific CD8 + T cells as detected by IFN-γ production, while only DCs stimulated with the antibody, induced the proliferation of allogeneic T cells similarly to mDCs. The difference in the profile of costimulatory molecules observed could make account for the distinct immunogenicity.…”

“…In other studies, C-type lectin activation resulted in the secretion of multiple cytokines and chemokines by DCs [32,34,35], even if the upregulation of costimulatory molecules was not always detected. Moreover, C-type lectin targeting increased DC cross-presentation or improved the activation by DCs of specific lymphocyte subsets [36,37].…”

Human Langerhans cells capture measles virus through Langerin and present viral antigens to CD4+ T cells but are incapable of cross‐presentation

“…Different studies have suggested a balance between efficient targeting of antigens for presentation in HLA-I or HLA-II [4,15,42]. Langerin internalizes antigens into Birbeck granules that might prevent antigens from entering the cross-presentation route or prevent triggering of pattern recognition receptors that could be required for cross-presentation [43].…”

“…Furthermore, MV-infected mature LCs are capable of presenting endogenous MV antigens in the context of HLA-I molecules. Taken together these results strongly suggest that capture of MV by primary LCs results in presentation of antigens in the context of HLA-II molecules, but does not lead to cross-presentation of MV to CD8 1 T cells.Different studies have suggested a balance between efficient targeting of antigens for presentation in HLA-I or HLA-II [4,15,42]. Langerin internalizes antigens into Birbeck granules that might prevent antigens from entering the cross-presentation route or prevent triggering of pattern recognition receptors that could be required for cross-presentation [43].…”

“…However, the ability of LCs to cross-present exogenous antigens to CD8 1 T cells has been debated [14][15][16][17]. Klechevsky et al [13] have shown that in vitrogenerated human LCs from either CD34 1 cells or monocytes are capable of cross-presenting influenza-virus proteins to CD8 1 T cells.…”