Thymocyte sensitivity and supramolecular activation cluster formation are developmentally regulated: a partial role for sialylation.
TCR reactivity is tuned during thymic development. Immature thymocytes respond to low-affinity self-ligands resulting in positive selection. Following differentiation, T cells no longer respond to low-affinity ligands, but respond well to high-affinity (foreign) ligands. We show in this study that this response includes integrin activation, supramolecular activation cluster formation, Ca(2+) flux, and CD69 expression. Because glycosylation patterns are known to change during T cell development, we tested whether alterations in sialylation influence CD8 T cell sensitivity to low affinity TCR ligands. Using neuraminidase treatment or genetic deficiency in the ST3Gal-I sialyltransferase, we show that desialylation of mature CD8 T cells enhances their sensitivity to low-affinity ligands, although these treatments do not completely recapitulate the dynamic range of immature T cells. These studies identify sialylation as one of the factors that regulate CD8 T cell tuning during development.
Center for Immunology, Laboratory of Medicine and Pathology, University of Minnesota, Minneapolis MN 55455, USA.
Timothy K
TK
Starr
Mark A
MA
Daniels
Michelle M
MM
Lucido
Stephen C
SC
Jameson
Kristin A
KA
Hogquist
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D002449:Cell Aggregation / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D006706:Homeostasis / Q000235:genetics / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D019158:N-Acetylneuraminic Acid / Q000378:metabolism*; D009924:Organ Culture Techniques; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D012799:Sialyltransferases / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism*; D013950:Thymus Gland / Q000166:cytology / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism*; D015854:Up-Regulation / Q000276:immunology; D000094663:beta-Galactoside alpha-2,3-Sialyltransferase
D011948:Receptors, Antigen, T-Cell; D012799:Sialyltransferases; D019158:N-Acetylneuraminic Acid; D000094663:beta-Galactoside alpha-2,3-Sialyltransferase