Characterization of the human beta -glucan receptor and its alternatively spliced isoforms.
beta-1,3-d-Glucans are biological response modifiers with potent effects on the immune system. A number of receptors are thought to play a role in mediating these responses, including murine Dectin-1, which we recently identified as a beta-glucan receptor. In this study we describe the characterization of the human homologue of this receptor and show that it is structurally and functionally similar to the mouse receptor. The human beta-glucan receptor is a type II transmembrane receptor with a single extracellular carbohydrate recognition domain and an immunoreceptor tyrosine activation motif in its cytoplasmic tail. The human beta-glucan receptor is widely expressed 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 spliced, resulting in two major (A and B) and six minor isoforms. The two major isoforms differ by the presence of a stalk region separating the carbohydrate recognition domain from the transmembrane region and are the only isoforms that are functional for beta-glucan binding. The human receptor also binds T-lymphocytes at a site distinct from the beta-glucan binding site, indicating that this receptor can recognize both endogenous and exogenous ligands.
Willment
J A
JA
Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford, OX1 3RE, United Kingdom.
Gordon
S
S
Brown
G D
GD
D017398:Alternative Splicing; D000818:Animals; D001483:Base Sequence; D002175:Candida / Q000378:metabolism; D002460:Cell Line; D003001:Cloning, Molecular; D017931:DNA Primers; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D011485:Protein Binding; D011971:Receptors, Immunologic / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000378:metabolism
D017931:DNA Primers; D011971:Receptors, Immunologic; C045268:beta-glucan receptor