Journal
JOURNAL OF IMMUNOLOGY
Volume 171, Issue 9, Pages 4512-4520Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.171.9.4512
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Funding
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [T32AI007313, R01AI039560, R01AI052163] Funding Source: NIH RePORTER
- NIAID NIH HHS [R01-AI39560, AI52163, 2T32-AI07313] Funding Source: Medline
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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, Ca2+ 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.
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