Distribution and Function of Macrophage Galactose-type C-type Lectin 2 (MGL2/CD301b)

Abstract

Dendritic cells (DCs) express cell surface lectins that are potentially involved in the recognition, uptake, and presentation of glycosylated foreign substances. A unique calcium-type (C-type) lectin, the macrophage galactose (Gal)-type C-type lectin (MGL/CD301) expressed on DCs, is thought to participate in the recognition of molecules from both altered self and pathogens due to its monosaccharide specificity for Gal and N-acetylgalactosamine (GalNAc). Although mice have two MGL genes, Mgl1 and Mgl2, their distinct roles have not been previously explored. The present report characterizes the properties of MGL2 by examining its distribution and its role in antigen presentation by DCs. We generated an MGL2-specific monoclonal antibody and examined MGL2 expression in tissues by immunohistochemistry and in isolated cells by flow cytometry. The cells reactive with this antibody were shown to be a portion of MGL1-expressing cells, mostly conventional DCs. Internalization of soluble polyacrylamide polymers (PAA) with ␣-GalNAc residues (GalNAc-PAA) by bone marrow-derived DCs (BM-DCs) was mediated by MGL2, as revealed by a comparison of Mgl1 ؊/؊ and Mgl2 ؊/؊ BM-DCs with wild-type BM-DCs. Biotinylated GalNAc-PAA conjugated to streptavidin (SAv) was more efficiently presented to SAv-primed T cells by BM-DCs than ␤-N-acetylglucosamine-PAA conjugated to SAv or SAv alone as shown by thymidine uptake and cytokine production. This is the first report that demonstrates the involvement of GalNAc residues in antigen uptake and presentation by DCs that lead to CD4 ؉ T cell activation.

CD301b + Mononuclear Phagocytes Maintain Positive Energy Balance through Secretion of Resistin-like Molecule Alpha

“…Indeed, a fraction of CD11b + F4/80 int to high macrophage-like cells in the visceral adipose tissue, as well as other metabolic organs, expressed CD301b protein (Figure 1B). Importantly, as was observed previously with the CD301b + cells in other sites of the body (Denda-Nagai et al, 2010; Kumamoto et al, 2009; Kumamoto et al, 2013), the majority of CD301b + cells in the peripheral organs uniformly expressed a high amount of MHC class II and CD11b, an intermediate to high amount of CD11c, and only a moderate amount of F4/80 (Figure 1A, B). …”

Modification of Asparagine-Linked Glycan Density for the Design of Hepatitis B Virus Virus-Like Particles with Enhanced Immunogenicity

“…An enhanced uptake of hyperglycosylated VLPs derived from the rabbit hemorrhagic disease virus (RHDV) by antigen-presenting cells strongly indicates that the interaction between an antigen and immune cells can be modified depending on the glycosylation status of the antigen (38). Utilizing glycans and targeting lectin receptors to promote antigen uptake and presentation is a promising path to enhance subsequent antigen-specific immune responses (40,46,64).…”

Chemical Lectinology: Tools for Probing the Ligands and Dynamics of Mammalian Lectins In Vivo

“…Phosphorylation of JNK was not seen in other studies of DC-SIGN binding, leading to the proposal that DC-SIGN reorganization and perhaps clustering is necessary for signaling to take place. C-type lectin-dependent uptake may be a general feature in antigen processing, as polyacrylamide (PAA)-GalNAc glycopolymers were found by Irimura and coworkers to be readily internalized by DCs through Macrophage Galactose-type C-type Lectin 2 (MGL2) (Denda-Nagai et al, 2010). …”