The HB-6, CDw75, and CD76 differentiation antigens are unique cell-surface carbohydrate determinants generated by the beta-galactoside alpha 2,6-sialyltransferase.
Expression of the beta-galactoside alpha 2,6-sialyltransferase (alpha 2,6-ST) was shown to regulate the generation of multiple cell-surface differentiation antigens (Ags) that may be necessary for lymphocyte function. A new mAb was produced, termed HB-6, that was shown to identify a novel neuraminidase-sensitive cell-surface Ag expressed by subpopulations of human lymphocytes and erythrocytes. In attempting to isolate a cDNA encoding the HB-6 antigen by expression cloning, a cDNA encoding the alpha 2,6-ST (EC 2.4.99.1) was obtained. Since expression of the alpha 2,6-ST protein was shown to be limited to the Golgi apparatus, the cell-surface HB-6 Ag was demonstrated to be the product of alpha 2,6-ST activity. Interestingly, alpha 2,6-ST expression also generated two other neuraminidase-sensitive lymphocyte cell-surface differentiation Ags, CDw75, and CD76. The HB-6, CDw75, and CD76 mAb identified distinct Ags that were differentially expressed by different B cell lines and exhibited different patterns of expression in tissue sections. These results indicate that alpha 2,6-ST expression is a critical regulatory step in the formation of the Ags that are recognized by these mAb, and that an alpha 2,6-linked sialic acid residue is an essential component of each Ag. Thus, expression of a single ST can result in the generation of multiple distinct antigenic determinants on the cell surface which can be distinguished by mAb and may have regulatory roles in lymphocyte function.
Bast
B J
BJ
Division of Tumor Immunology, Dana-Farber Cancer Institute, Boston, Massachusetts.
Zhou
L J
LJ
Freeman
G J
GJ
Colley
K J
KJ
Ernst
T J
TJ
Munro
J M
JM
Tedder
T F
TF
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000943:Antigens, Differentiation / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D000954:Antigens, Surface / Q000378:metabolism*; D001483:Base Sequence; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics; D005434:Flow Cytometry; D006056:Golgi Apparatus / Q000201:enzymology; D006801:Humans; D008969:Molecular Sequence Data; D009439:Neuraminidase / Q000494:pharmacology; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D015183:Restriction Mapping; D012799:Sialyltransferases / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology; D014407:Tumor Cells, Cultured / Q000276:immunology; D000094802:beta-D-Galactoside alpha 2-6-Sialyltransferase
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000943:Antigens, Differentiation; D000954:Antigens, Surface; C063411:CD76 antigen; D009838:Oligodeoxyribonucleotides; C072272:HB-6 antigen; D004247:DNA; D012799:Sialyltransferases; C093493:ST6GAL1 protein, human; D009439:Neuraminidase; D000094802:beta-D-Galactoside alpha 2-6-Sialyltransferase