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.

The HLA-B∗15:02 allele has been reported to have a strong association with carbamazepine-induced Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) in Thai patients. The HLA-B alleles associated with carbamazepine-induced maculopapular exanthema (MPE) and the drug reaction with eosinophilia and systemic symptoms (DRESS) among the Thai population have never been reported. The aim of the present study was to carry out an analysis of the involvement of HLA-B alleles in carbamazepine-induced cutaneous adverse drug reactions (cADRs) in the Thai population. A case-control study was performed by genotyping the HLA-B alleles of Thai carbamazepine-induced hypersensitivity reaction patients (17 MPE, 16 SJS/TEN, and 5 DRESS) and 271 carbamazepine-tolerant controls. We also recruited 470 healthy Thai candidate subjects who had not taken carbamazepine. HLA-B∗15:02 showed a significant association with carbamazepine-induced MPE (P = 0.0022, odds ratio (OR) (95% confidence interval [CI]) = 7.27 (2.04–25.97)) and carbamazepine-induced SJS/TEN (P = 4.46 × 10−13; OR (95% CI) = 70.91(19.67–255.65)) when compared with carbamazepine-tolerant controls. Carbamazepine-induced SJS/TEN also showed an association with HLA-B∗15:21 allele (P = 0.013; OR (95% CI) = 9.54 (1.61–56.57)) when compared with carbamazepine-tolerant controls. HLA-B∗58:01 allele was significantly related to carbamazepine-induced MPE (P = 0.007; OR (95% CI) = 4.73 (1.53–14.66)) and DRESS (P = 0.0315; OR (95% CI) = 7.55 (1.20–47.58)) when compared with carbamazepine-tolerant controls. These alleles may serve as markers to predict carbamazepine-induced cADRs in the Thai population.

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Macrophage galactose-type C-type lectins 1 and 2 (MGL1/2) are expressed on the surfaces of macrophages and immature dendritic cells. Despite the high similarity between the primary sequences of MGL1 and MGL2, they display different ligand specificities. MGL1 shows high affinity for the Lewis X trisaccharide, whereas MGL2 shows affinity for N-acetylgalactosamine. To elucidate the structural basis for the ligand specificities of the MGLs, we performed NMR analyses of the MGL1-Lewis X complex. To identify the Lewis X binding site on MGL1, a saturation transfer experiment for the MGL1-Lewis X complex where sugar-CH/CH 2 -selective saturation was applied was carried out. To obtain sugar moiety-specific information on the interface between MGL1 and the Lewis X trisaccharide, saturation transfer experiments where each of galactose-H5-, fucose-CH 3 -, and N-acetylglucosamine-CH 3 -selective saturations was applied to the MGL1-Lewis X complex were performed. Based on these results, we present a Lewis X binding mode on MGL1 where the galactose moiety is bound to the primary sugar binding site, including Asp-94, Trp-96, and Asp-118, and the fucose moiety interacts with the secondary sugar binding site, including Ala-89 and Thr-111. Ala-89 and Thr-111 in MGL1 are replaced with arginine and serine in MGL2, respectively. The hydrophobic environment formed by a small side chain of Ala-89 and a methyl group of Thr-111 is a requisite for the accommodation of the fucose moiety of the Lewis X trisaccharide within the sugar binding site of MGL1. Macrophage galactose (Gal)2 -type calcium-type (C-type) lectins (MGLs; CD301) are carbohydrate recognition proteins expressed on the surfaces of macrophages and immature dendritic cells in humans and rodents (1-4). In mice, two closely related MGLs, MGL1 and MGL2 (CD301a and CD301b), have been found (3), whereas humans have a single MGL (CD301) gene (2). MGLs have unique carbohydrate specificities toward galactose and N-acetylgalactosamine as monosaccharides, whereas many other C-type lectins on macrophages and dendritic cells have the mannose (Man)-type specificity, such as DC-SIGN and the macrophage mannose receptor (5). The cells expressing MGL1 are widely distributed in connective tissues (6). A variety of biological functions of MGL1 have been reported so far, such as the recognition and endocytosis of glycoproteins with terminal Gal/GalNAc moieties (7, 8), contribution to defense against tumor cell metastasis (9, 10), and clearance of apoptotic cells in embryos (11,12). MGL2 is also expressed on the cells that display the same distribution pattern as MGL1-positive cells (3). For human MGL, additional functions, involvements in the regulation of effector T cells (13) and the promotion of filovirus entry (14), have been reported.The MGL molecules are ϳ42-kDa type II transmembrane glycoproteins, which possess a cytoplasmic domain, a transmembrane domain, a neck domain, and a carbohydrate recognition domain (CRD) within each molecule (1, 3). Two potential N-glycosylation sites are present...

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