A distinct type of sialyl Lewis X antigen defined by a novel monoclonal antibody is selectively expressed on helper memory T cells.
A subset of human helper memory T cells is known to adhere to E-selectin expressed on cytokine-activated endothelial cells. However, sialyl Lex antigen, the carbohydrate ligand for E-selectin, has been hardly detectable on these cells, at least when typical anti-sialyl Lex antibodies were used for detection. One of the MoAbs (2F3, IgM), which we raised against a chemically synthesized sialyl Lex glycolipid preparation, is found to react selectively to CD4+ CD45RObright+ CD45RA- helper memory T cells among peripheral lymphocytes in healthy individuals. The specificity of the antibody is in clear contrast to that of the hitherto reported typical anti-sialyl Lex antibodies FH-6 and SNH-3. These classical anti-sialyl Lex antibodies were known to react to a subset of natural killer (NK) cells, but were not reactive with any particular subset of resting peripheral T or B cells of healthy individuals if the cells were not activated. On the other hand, the newly generated 2F3 antibody specifically reacted to helper memory T cells, and did not react to NK cells, B cells, or any T cells other than helper memory T cells. When tested against the sialyl Lex-active glycolipid antigen, the reactivity of 2F3 was not significantly different from that of the classical anti-sialyl Lex antibodies. But when tested against oligosaccharides prepared from cellular glycoproteins, 2F3 detected a distinct set of O-linked oligosaccharides, which were not reactive to the classical anti-sialyl Lex antibodies. Our results suggest that various molecular species of sialyl Lex antigens are present on carbohydrate side chains of cellular glycoproteins, and that helper memory T cells express a distinct type of sialyl Lex antigen that is defined by 2F3 but is not efficiently detected by other typical anti-sialyl Lex antibodies. Among cultured lymphocytic leukemia cells, the adult T-cell leukemia (ATL) cells preferentially expressed the 2F3-defined antigen, and acute lymphocytic leukemia cells rarely expressed the antigen. The cultured ATL cells expressing the 2F3-defined antigen showed a clear E-selectin-dependent adhesion to cytokin-activated endothelial cells, and the 2F3-defined sialyl Lex antigen served as a ligand for E-selectin as ascertained by the clear inhibition of adhesion with the 2F3 antibody.(ABSTRACT TRUNCATED AT 400 WORDS)
Ohmori
K
K
Department of Laboratory Medicine, Kyoto University, School of Medicine, Japan.
Takada
A
A
Ohwaki
I
I
Takahashi
N
N
Furukawa
Y
Y
Maeda
M
M
Kiso
M
M
Hasegawa
A
A
Kannagi
M
M
Kannagi
R
R
D000911:Antibodies, Monoclonal / Q000276:immunology*; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002478:Cells, Cultured; D019040:E-Selectin; D006801:Humans; D007156:Immunologic Memory; D015458:Leukemia, T-Cell / Q000276:immunology; D017254:Leukemic Infiltration; D017493:Leukocyte Common Antigens / Q000032:analysis; D016256:Lewis X Antigen / Q000032:analysis* / Q000276:immunology / Q000502:physiology; D012867:Skin / Q000473:pathology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D019040:E-Selectin; D016256:Lewis X Antigen; D017493:Leukocyte Common Antigens