Regulation of CD45 engagement by the B-cell receptor CD22.
The B-cell receptor CD22 binds sialic acid linked alpha-2-6 to terminal galactose residues on N-linked oligosaccharides associated with several cell-surface glycoproteins. The first of these sialoglycoproteins to be identified was the receptor-linked phosphotyrosine phosphatase CD45, which is required for antigen/CD3-induced T-cell activation. In the present work, we examine the effect of interaction between the extracellular domain of CD45 and CD22 on T-cell activation. Using soluble CD22-immunoglobulin fusion proteins and T cells expressing wild-type and chimeric CD45 forms, we show that engagement of CD45 by soluble CD22 can modulate early T-cell signals in antigen receptor/CD3-mediated stimulation. We also show that addition of sialic acid by beta-galactoside alpha-2,6-sialyltransferase to the CD22 molecule abrogates interactions between CD22 and its ligands. Together, these observations provide direct evidence for a functional role of the interaction between the extracellular domain of CD45 and a natural ligand and suggest another regulatory mechanism for CD22-mediated ligand engagement.
Sgroi
D
D
Department of Pathology, Massachusetts General Hospital, Boston, USA.
Koretzky
G A
GA
Stamenkovic
I
I
D015703:Antigens, CD / Q000378:metabolism*; D000944:Antigens, Differentiation, B-Lymphocyte / Q000378:metabolism*; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002460:Cell Line; D006801:Humans; D007295:Inositol Phosphates / Q000378:metabolism*; D007527:Isoenzymes / Q000378:metabolism; D007700:Kinetics; D037102:Lectins; D017493:Leukocyte Common Antigens / Q000378:metabolism*; D010766:Phosphorylation; D019000:Phosphotyrosine; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000378:metabolism; D051918:Sialic Acid Binding Ig-like Lectin 2; D012799:Sialyltransferases / Q000378:metabolism; D010738:Type C Phospholipases / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives / Q000032:analysis; D000094802:beta-D-Galactoside alpha 2-6-Sialyltransferase
D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; C497867:CD22 protein, human; D015815:Cell Adhesion Molecules; D007295:Inositol Phosphates; D007527:Isoenzymes; D037102:Lectins; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D051918:Sialic Acid Binding Ig-like Lectin 2; D019000:Phosphotyrosine; D014443:Tyrosine; D012799:Sialyltransferases; D017493:Leukocyte Common Antigens; D010738:Type C Phospholipases; D002118:Calcium; D000094802:beta-D-Galactoside alpha 2-6-Sialyltransferase