Characterization of the human beta-glucan receptor and its alternatively spliced isoforms

beta -1,3-D-Glucans are biological response modifiers with potent effects o n the immune system. A number of receptors are thought to play a role in me diating these responses, including murine Dectin-1, which we recently ident ified as a beta -glucan receptor. In this study we describe the characteriz ation of the human homologue of this receptor and show that it is structura lly and functionally similar to the mouse receptor. The human beta -glucan receptor is a type II transmembrane receptor with a single extracellular ca rbohydrate recognition domain and an immunoreceptor tyrosine activation mot if in its cytoplasmic tail. The human beta -glucan receptor is widely expre ssed and functions as a pattern recognition receptor, recognizing a variety of beta -1,3- and/or beta -1,6-linked glucans as well as intact yeast. In contrast to the murine receptor, the human receptor mRNA is alternatively s pliced, resulting in two major (A and B) and six minor isoforms. The two ma jor isoforms differ by the presence of a stalk region separating the carboh ydrate recognition domain from the transmembrane region and are the only is oforms that are functional for beta -glucan binding. The human receptor als o binds T-lymphocytes at. a site distinct from the beta -glucan binding sit e, indicating that this receptor can recognize both endogenous and exogenou s ligands.