CLEC18 family are novel C-type lectins with differential binding specificity to glycans and TLR ligands

Abstract

Abstract The human C-type lectin 18 (clec18) gene cluster, which contains clec18a, clec18b and clec18c three loci, is located in human chromosome 16q22. Even though the amino acid sequences of CLEC18A, CLEC18B, and CLEC18C are almost identical, several amino acid residues located in the C-type lectin-like domain (CTLD) and the Sperm-Coating Protein/Tpx-1/Ag5/PR-1/Sc7 (SCP/TAPS) domain, also known as the cysteine-rich secretory proteins/antigen 5/pathogenesis-related 1 proteins (CAP) domain, are distinct from each other. Genotyping by real-time PCR and sequencing further shows the presence of multiple alleles in clec18a/b/c loci. Flow cytometry analysis demonstrates that CLEC18 (CLEC18A, B and C) are expressed abundantly in human peripheral blood cells. Moreover, CLEC18 expression is further upregulated when monocytes differentiate into macrophages and dendritic cells (DCs). Immunofluorescence staining reveals that CLEC18 are localized in the endoplasmic reticulum (ER), Golgi apparatus, and endosome. Interestingly, CLEC18 are also detectable in human sera and culture supernatants from primary cells and 293T cells overexpressing CLEC18. Moreover, CLEC18 bind polysaccharide in Ca2+–independent manner, and the amino acid residues S/R339 and D/N421 in CTLD domain contribute to their differential binding abilities to polysaccharides isolated from Ganoderma lucidum (GLPS-F3). The S339 (CLEC18A) and R339 (CLEC18A-1) displayed differential binding affinity to TLR ligands. Their roles to determine host responses to virus infection are under intensive investigation now.