Identification of a human homologue of the dendritic cell-associated C-type lectin-1, dectin-1.

Previously we identified the novel type II lectin receptor, dectin-1, that is expressed preferentially by murine antigen presenting dendritic cells (DC) and is involved in co-stimulation of T cells by DC. To identify the human homologue (DECTIN-1), we employed degenerative PCR amplification of mRNA isolated from DC and subsequent cDNA cloning. DECTIN-1 is a type II lectin receptor with high homology to type II lectin receptors expressed by natural killer (NK) cells. It contains an immunoreceptor tyrosine-based activation motif within the cytoplasmic domain. Human DECTIN-1 mRNA is expressed predominantly by peripheral blood leukocytes and preferentially by DC. The mRNA likely encodes a 33 kDa glycoprotein. In human epidermis, the protein is expressed selectively by Langerhans cells, which are an epidermal subset of DC. A truncated form of DECTIN-1 RNA (termed T beta) encodes for a polypeptide lacking almost the entire neck domain, which is required for accessibility of the carbohydrate recognition domain to ligands. Genome analysis showed the deleted amino acid sequence in T beta to be encoded by an exon, indicating that T beta RNA is produced by alternative splicing. DECTIN-1 gene maps to chromosome 12, between p13.2 and p12.3, close to the NK gene complex (12p13.1 to p13.2) which contains genes for NK lectin receptors. Our results indicate that human DECTIN-1 shares many features with mouse dectin-1, including the generation of neck domain-lacking isoforms, which may down-regulate the co-stimulatory function of dectin-1.