The mannose receptor functions as a high capacity and broad specificity antigen receptor in human dendritic cells

Abstract

Dendritic cells, in contrast to B lymphocytes, must be able to efficiently internalize a diverse array of antigens for processing and loading onto major histocompatibility complex (MHC) class II molecules. Here we characterize the mannose receptor pathway in dendritic cells and show that mannose receptor-mediated uptake of antigens results in a approximately 100-fold more efficient presentation to T cells, as compared to antigens internalized via fluid phase. Immunocytochemistry as well as subcellular fractionation revealed the localization of the mannose receptor and MHC class II molecules in distinct subcellular compartments. The mannose receptor thus functions in rapid internalization and concentration of a variety of glycosylated antigens that become available for processing and presentation. This may contribute to the unique capacity of dendritic cells to generate primary T cell responses against infectious agents.

Delivery of antigen using a novel mannosylated dendrimer potentiates immunogenicity in vitro and in vivo

“…It has been previously shown that mannosylated antigens are internalized and processed following the endocytic pathway, leading to enhanced MHC class II presentation of antigenic peptides [4,5]. In our studies, we show that MD greatly enhances the delivery of OVA into both MHC class I-and II-presentation pathways in BMDC (Fig.…”

“…Uptake of antigens via these receptors on the APC surface is followed by delivery into the endolysosomal pathway, leading to MHC-class II presentation [4]. In comparison to antigens internalized via the fluid phase (e.g., pinocytosis), this pathway of antigen uptake in DC results in a considerable increase of efficiency in antigen presentation and T cell stimulation [5][6][7][8]. For instance, it was shown that antigen uptake mediated by mannosebinding receptors increased antigen presentation to T cells up to 100-fold [5].…”

“…In comparison to antigens internalized via the fluid phase (e.g., pinocytosis), this pathway of antigen uptake in DC results in a considerable increase of efficiency in antigen presentation and T cell stimulation [5][6][7][8]. For instance, it was shown that antigen uptake mediated by mannosebinding receptors increased antigen presentation to T cells up to 100-fold [5]. Mannosylated antigens were efficiently internalized by DC and localized in the MHC class II-specific compartments and lysosomes, resulting in 200-10 000-fold enhanced potency in stimulating specific MHC class II-restricted T cells [8].…”

C‐reactive protein impairs human CD14+ monocyte‐derived dendritic cell differentiation, maturation and function

“…This 205-kD protein contains C-type lectin domains and is a homologue to the MR CD206. In fact, both the MR [47,48] and DEC-205 [49,50] mediate antigen uptake. CD205 expression on human DC is up-regulated upon maturation, and this endocytic receptor is involved in both antigen uptake and processing.…”

Matrix metalloproteinase 12 silencing: A therapeutic approach to treat pathological lung tissue remodeling?

“…This observation could be applied to antibodies or aptamers -siRNA conjugates. Targeting macrophages, that are the principal source of MMP-12 production, can be assessed by exploiting the mannose-binding receptor that mediates the non-opsonic phagocytic uptake by macrophages [126] and the endocytosis of soluble glycoconjugates leading to enhanced uptake of ligands [127]. However, other classes of phagocytic-inducing receptors also expressed on macrophage surface can be investigated.…”