Alteration of cell surface sialylation regulates antigen-induced naive CD8+ T cell responses.
The strength of interactions with APC instructs naive T cells to undergo programmed expansion and differentiation, which is largely determined by the peptide affinity and dose as well as the duration of TCR ligation. Although, most ligands mediating these interactions are terminally sialylated, the impact of the T cell sialylation status on Ag-dependent response remains poorly understood. In this study, by monitoring TCR transgenic CD8+ T cells, OT-I, we show that biochemical desialylation of naive OT-I T cells increases their sensitivity for agonist as well as partial agonist peptides. Desialylation enhances early activation and shortens the duration of TCR stimulation required for proliferation and differentiation, without increasing apoptosis. Moreover, desialylation of naive OT-I T cells augments their response to tumor-presented Ag. These results provide direct evidence for a regulatory role for sialylation in Ag-dependent CD8+ T cell responses and offer a new approach to sensitize or dampen Ag-specific CD8+ T cell responses.
Pappu
Bhanu P
BP
Department of Immunology, Roswell Park Cancer Institute, 322 Comprehensive Cancer Center, Elm & Carlton Streets, Buffalo, NY 14263, USA.
Shrikant
Protul A
PA
D000818:Animals; D000938:Antigen-Presenting Cells / Q000502:physiology; D015703:Antigens, CD / Q000032:analysis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D017209:Apoptosis; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005452:Fluoresceins / Q000378:metabolism; D007371:Interferon-gamma / Q000096:biosynthesis; D037181:Lectins, C-Type; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D019158:N-Acetylneuraminic Acid / Q000378:metabolism*; D013388:Succinimides / Q000378:metabolism; D000099192:CD69 Antigens
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D005452:Fluoresceins; D007371:Interferon-gamma; D037181:Lectins, C-Type; D019158:N-Acetylneuraminic Acid; D013388:Succinimides; D000099192:CD69 Antigens; C087165:5-(6)-carboxyfluorescein diacetate succinimidyl ester