|
|
|
|
|
|
|
||
By
From the Glycobiology Program, UCSD Cancer Center, the Department of Medicine, University of
California, San Diego, La Jolla, California 92093
Terminal sialic acids on cell surface glycoconjugates can carry 9-O-acetyl esters. For technical
reasons, it has previously been difficult to determine their precise distribution on different cell
types. Using a recombinant soluble form of the Influenza C virus hemagglutinin-esterase as a
probe for 9-O-acetylated sialic acids, we demonstrate here their preferential expression on the CD4 T cell lineage in normal B10.A mouse lymphoid organs. Of total thymocytes, 8-10%
carry 9-O-acetylation; the great majority of these are the more mature PNA
, HSA, and
TCRhi medullary cells. While low levels of 9-O-acetylation are seen on some CD4/CD8 double positive (DP) and CD8 single positive (SP) cells, high levels are present primarily on 80-
85% of CD4 SP cells. Correlation with CD4 and CD8 levels suggests that 9-O-acetylation appears as an early differentiation marker as cells mature from the DP to the CD4 SP phenotype.
This high degree of 9-O-acetylation is also present on 90-95% of peripheral spleen and lymph
node CD4 T cells. In contrast, only a small minority of CD8 T cells and B cells show such levels of 9-O-acetylation. Among mature peripheral CD4 T lymphocytes, the highly O-acetylated
cells are Mel 14hi, CD44lo, and CD45R(exon B)hi, features typical of naive cells. Digestions with
trypsin and O-sialoglycoprotease (OSGPase) and ELISA studies of lipid extracts indicate that the
9-O-acetylated sialic acids on peripheral CD4 T cells are predominantly on O-linked mucintype glycoproteins and to a lesser degree, on sialylated glycolipids (gangliosides). In contrast,
sialic acids on mucin type molecules of CD8 T cells are not O-acetylated; instead these molecules mask the recognition of O-acetylated gangliosides that seem to be present at similar levels as
on CD4 cells. The 9-O-acetylated gangliosides on mouse T cells are not bound by CD60 antibodies, which recognize O-acetylated gangliosides in human T cells. Tethering 9-O-acetylated
mucins with the Influenza C probe with or without secondary cross-linking did not cause activation of CD4 T cells. However, activation by other stimuli including TCR ligation is associated with a substantial decrease in surface 9-O-acetylation, primarily in the mucin glycoprotein component. Thus, 9-O-acetylation of sialic acids on cell surface mucins is a novel marker on
CD4 T cells that appears on maturation and is modulated downwards upon activation.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
| TABLE OF CONTENTS |
|
