The DC-SIGN family member LSECtin is a novel ligand of CD44 on activated T cells.
LSECtin, a novel member of the C-type lectin DC-SIGN family, not only acts as an attachment factor for pathogens, but also recognizes "endogenous" activated T cells. The endogenous ligands of LSECtin, however, have remained unclear. In this study, we identified CD44 on Jurkat T cells as a candidate ligand of LSECtin, and confirmed the specific interaction between LSECtin and CD44. Moreover, we showed that LSECtin selectively bound CD44s, CD44v4 and CD44v8-10 by screening a series of typical CD44 isoforms. By deletion of the carbohydrate-recognition domain region and mutation of crucial amino acids involved in carbohydrate-recognition of LSECtin and by inhibition of the N-linked glycosylation of CD44, we further demonstrated that the interaction between CD44 and LSECtin is dependent on protein-glycan recognition. Our findings indicate that CD44 is the first identified endogenous ligand of LSECtin, and similarly, that LSECtin is a novel ligand of CD44. These findings provide important new perspectives on the biology of both LSECtin and CD44 in the immune system.
Tang
Li
L
State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing, P R China.
Yang
Juntao
J
Tang
Xiaoming
X
Ying
Wantao
W
Qian
Xiaohong
X
He
Fuchu
F
D000595:Amino Acid Sequence; D001665:Binding Sites; D002460:Cell Line; D006031:Glycosylation; D006801:Humans; D018960:Hyaluronan Receptors / Q000737:chemistry / Q000378:metabolism*; D015759:Ionomycin / Q000494:pharmacology; D019169:Jurkat Cells / Q000187:drug effects / Q000378:metabolism; D037181:Lectins, C-Type / Q000737:chemistry / Q000378:metabolism*; D008024:Ligands; D008213:Lymphocyte Activation / Q000187:drug effects; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009842:Oligopeptides / Q000032:analysis; D011134:Polysaccharides / Q000378:metabolism; D025941:Protein Interaction Mapping; D020033:Protein Isoforms / Q000737:chemistry / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
C497483:CD44 protein, human; C505228:CLEC4G protein, human; D018960:Hyaluronan Receptors; D037181:Lectins, C-Type; D008024:Ligands; D009842:Oligopeptides; D011134:Polysaccharides; D020033:Protein Isoforms; D011993:Recombinant Fusion Proteins; D015759:Ionomycin; D013755:Tetradecanoylphorbol Acetate