Starr Timothy K, Daniels Mark A, Lucido Michelle M, Jameson Stephen C, Hogquist Kristin A
Center for Immunology, Laboratory of Medicine and Pathology, University of Minnesota, Minneapolis MN 55455, USA.
J Immunol. 2003 Nov 1;171(9):4512-20. doi: 10.4049/jimmunol.171.9.4512.
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.
