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Characterization of ß-Glucan Recognition Site on C-Type Lectin, Dectin 1

Laboratory for Immunopharmacology of Microbial Products, School of Pharmacy, Tokyo University of Pharmacy and Life Science, Hachioji,¹ Seikagaku Corporation, Higashiyamato, Tokyo, Japan²

Received 14 February 2004/ Returned for modification 1 March 2004/ Accepted 5 April 2004

Dectin 1 is a mammalian cell surface receptor for (13)-ß-D-glucans. Since (13)-ß-D-glucans are commonly present on fungal cell walls, it has been suggested that dectin 1 is important for recognizing fungal invasion. In this study we tried to deduce the amino acid residues in dectin 1 responsible for ß-glucan recognition. HEK293 cells transfected with mouse dectin 1 cDNA could bind to a gel-forming (13)-ß-D-glucan, schizophyllan (SPG). The binding of SPG to a dectin 1 transfectant was inhibited by pretreatment with other ß-glucans having a (13)-ß-D-glucosyl linkage but not by pretreatment with -glucans. Dectin 1 has a carbohydrate recognition domain (CRD) consisting of six cysteine residues that are highly conserved in C-type lectins. We prepared 32 point mutants with mutations in the CRD and analyzed their binding to SPG. Mutations at Trp²²¹ and His²²³ resulted in decreased binding to ß-glucan. Monoclonal antibody 4B2, a dectin- 1 monoclonal antibody which had a blocking effect on the ß-glucan interaction, completely failed to bind the dectin-1 mutant W221A. A mutant with mutations in Trp²²¹ and His²²³ did not have a collaborative effect on Toll-like receptor 2-mediated cellular activation in response to zymosan. These amino acid residues are distinct from residues in other sugar-recognizing peptide sequences of typical C-type lectins. These results suggest that the amino acid sequence W221-I222-H223 is critical for formation of a ß-glucan binding site in the CRD of dectin 1.

Editor: T. R. Kozel

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