title: Functional evaluation of activation-dependent alterations in the sialoglycan composition of T cells.
abstract: Sialic acids (Sias) are often conjugated to the termini of cellular glycans and are key mediators of cellular recognition. Sias are nine-carbon acidic sugars, and, in vertebrates, the major species are N-acetylneuraminic acid (Neu5Ac) and N-glycolylneuraminic acid (Neu5Gc), differing in structure at the C5 position. Previously, we described a positive feedback loop involving regulation of Neu5Gc expression in mouse B cells. In this context, Neu5Gc negatively regulated B-cell proliferation, and Neu5Gc expression was suppressed upon activation. Similarly, resting mouse T cells expressed principally Neu5Gc, and Neu5Ac was induced upon activation. In the present work, we used various probes to examine sialoglycan expression by activated T cells in terms of the Sia species expressed and the linkages of Sias to glycans. Upon T-cell activation, sialoglycan expression shifted from Neu5Gc to Neu5Ac, and the linkage shifted from α2,6 to α2,3. These changes altered the expression levels of sialic acid-binding immunoglobulin-like lectin (siglec) ligands. Expression of sialoadhesin and Siglec-F ligands increased, and that of CD22 ligands decreased. Neu5Gc exerted a negative effect on T-cell activation, both in terms of the proliferative response and in the context of activation marker expression. Suppression of Neu5Gc expression in mouse T and B cells prevented the development of nonspecific CD22-mediated T cell-B cell interactions. Our results suggest that an activation-dependent shift from Neu5Gc to Neu5Ac and replacement of α2,6 by α2,3 linkages may regulate immune cell interactions at several levels.
authors.affiliation: From the Laboratory of Membrane Biochemistry and Biophysics and.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Naito-Matsui
authors.forename: Shuhei
authors.initials: S
authors.lastname: Takada
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Kano
authors.forename: Tomonori
authors.initials: T
authors.lastname: Iyoda
authors.forename: Manabu
authors.initials: M
authors.lastname: Sugai
authors.forename: Akira
authors.initials: A
authors.lastname: Shimizu
authors.forename: Kayo
authors.initials: K
authors.lastname: Inaba
authors.forename: Lars
authors.initials: L
authors.lastname: Nitschke
authors.forename: Takeshi
authors.initials: T
authors.lastname: Tsubata
authors.forename: Shogo
authors.initials: S
authors.lastname: Oka
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Kozutsumi
authors.forename: Hiromu
authors.initials: H
authors.lastname: Takematsu
mesh_terms: D000818:Animals; D015214:Antigens, Differentiation, Myelomonocytic / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D002450:Cell Communication / Q000502:physiology*; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000502:physiology; D008213:Lymphocyte Activation / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D051918:Sialic Acid Binding Ig-like Lectin 2 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D063265:Sialic Acid Binding Immunoglobulin-like Lectins; D012794:Sialic Acids / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism*
chemical_list: D015214:Antigens, Differentiation, Myelomonocytic; C497868:Cd22 protein, mouse; C078888:N-(O-acetyl)glycoloylneuraminic acid; D051918:Sialic Acid Binding Ig-like Lectin 2; D063265:Sialic Acid Binding Immunoglobulin-like Lectins; D012794:Sialic Acids; C443130:Siglecf protein, mouse
keywords: Germinal Center; Glycobiology; Glycoconjugate; Lectin; Sialic Acid; Sialic Acid Modification; Siglec; T Cell