Cloning of a second dendritic cell-associated C-type lectin (Dectin-2) andits alternatively spliced isoforms

Using a subtractive cDNA cloning strategy, we isolated previously five nove l genes that were expressed abundantly by the murine dendritic cell (DC) li ne XS52, but not by the J774 macrophage line. One of these genes encoded a unique, DC-associated C-type lectin, termed "dectin-1." Here we report the characterization of a second novel gene that was also expressed in a DC-spe cific manner. Clone 1B12 encoded a type II membrane-integrated polypeptide of 209 amino acids containing a single carbohydrate recognition domain moti f in the COOH terminus. The expression pattern of this molecule, termed "de ctin-2," was almost indistinguishable from that for dectin-1; that is, both were expressed abundantly at mRNA and protein levels by the XS52 DC line, but not by non-DC lines, and both were detected in spleen and thymus, as we ll as in skin resident DC (i.e. Langerhans cells). Interestingly, reverse t ranscriptase-polymerase chain reaction and immunoblotting revealed multiple bands of dectin-2 transcripts and proteins suggesting molecular heterogene ity. In fact, we isolated additional cDNA clones encoding two distinct, tru ncated dectin-2 isoforms. Genomic analyses indicated that a full-length dec tin-2 (alpha isoform) is encoded by 6 exons, whereas truncated isoforms (be ta and gamma) are produced by alternative splicing. We propose that dectin- 2 and its isoforms, together with dectin-1, represent a unique subfamily of DC-associated C-type lectins.