A Distinct Type of Sialyl Lewis X Antigen Defined by a Novel Monoclonal Antibody Is Selectively Expressed on Helper Memory T Cells

Abstract

AbstractA 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 glyco-lipid preparation, is found to react selectively to CD4+ CD45RObrigh+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. The 2F3-defined sialyl Lex antigen tended to be expressed on the ATL cells from the patients with dermal infiltration of leukemic cells more strongly than on the ATL cells from the patients without skin involvement, suggesting that the cell adhesion mediated by the 2F3-defined sialyl Lex antigen plays a role in the skin infiltration process of ATL cells.