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

Previously we identified the novel type 11 lectin receptor. dectin-1, that is expressed preferentially by murine antigen presenting dendritic cells (D C) and is involved in co-stimulation of T cells by DC. To identify the huma n homologue (DECTIN-1), we employed degenerative PCR amplification of mRNA isolated from DC and subsequent cDNA cloning. DECTIN-1 is a type 11 lectin receptor with high homology to type 11 lectin receptors expressed by natura l killer (NK) cells. It contains an immunoreceptor tyrosine-based activatio n motif within the cytoplasmic domain. Human DECTIN-1 mRNA is expressed pre dominantly by peripheral blood leukocytes and preferentially by DC. The mRN A 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 TO) 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 TP to be encoded by an exon. indicating that TP RNA is produced by alternative splicing. DECTIN-1 gene maps to chro mosome 12, between p13.2 and p12.3, close to the NK gene complex (12p13.1 t o p13.2) which contains genes for NK lectin receptors. Our results indicate that human DECTIN-1 shares many features with mouse dectin-1. including th e generation of neck domain-lacking isoforms, which may down-regulate the c o-stimulatory function of dectin-1. (C) 2001 Elsevier Science B.V. All righ ts reserved.