Carbohydrate profiling reveals a distinctive role for the C-type lectin MGL in the recognition of helminth parasites and tumor antigens by dendritic cells.
Dendritic cells (DCs) are key to the maintenance of peripheral tolerance to self-antigens and the orchestration of an immune reaction to foreign antigens. C-type lectins, expressed by DCs, recognize carbohydrate moieties on antigens that can be internalized for processing and presentation. Little is known about the exact glycan structures on self-antigens and pathogens that are specifically recognized by the different C-type lectins and how this interaction influences DC function. We have analyzed the carbohydrate specificity of the human C-type lectin macrophage galactose-type lectin (MGL) using glycan microarray profiling and identified an exclusive specificity for terminal alpha- and beta-linked GalNAc residues that naturally occur as parts of glycoproteins or glycosphingolipids. Specific glycan structures containing terminal GalNAc moieties, expressed by the human helminth parasite Schistosoma mansoni as well as tumor antigens and a subset of gangliosides, were identified as ligands for MGL. Our results indicate an endogenous function for DC-expressed MGL in the clearance and tolerance to self-gangliosides, and in the pattern recognition of tumor antigens and foreign glycoproteins derived from helminth parasites.
van Vliet
Sandra J
SJ
Department of Molecular Cell Biology & Immunology, VU Medical Center, Amsterdam, The Netherlands.
van Liempt
Ellis
E
Saeland
Eirikur
E
Aarnoudse
Corlien A
CA
Appelmelk
Ben
B
Irimura
Tatsuro
T
Geijtenbeek
Teunis B H
TB
Blixt
Ola
O
Alvarez
Richard
R
van Die
Irma
I
van Kooyk
Yvette
Y
D000818:Animals; D017951:Antigen Presentation; D000947:Antigens, Helminth / Q000276:immunology*; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000276:immunology*; D002241:Carbohydrates / Q000276:immunology*; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology*; D005690:Galactose / Q000276:immunology; D005947:Glucose / Q000276:immunology; D006023:Glycoproteins / Q000276:immunology; D006028:Glycosphingolipids / Q000276:immunology / Q000378:metabolism; D006801:Humans; D037181:Lectins, C-Type / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000276:immunology / Q000378:metabolism; D012550:Schistosoma mansoni / Q000276:immunology*
D000947:Antigens, Helminth; D015295:Antigens, Tumor-Associated, Carbohydrate; D002241:Carbohydrates; D006023:Glycoproteins; D006028:Glycosphingolipids; D037181:Lectins, C-Type; C506225:MGL lectin, human; D011956:Receptors, Cell Surface; D005947:Glucose; D005690:Galactose