Abstract
The CD8 coreceptor plays a crucial role in thymocyte and T cell sensitivity by binding to class I MHC and recruiting downstream signaling molecules to the TCR. Previous studies reported considerable changes in TCR-independent CD8/class I MHC binding (i.e., CD8 noncognate interactions) during T cell development, changes that correlated with altered glycosylation of surface molecules. In particular, expression of the sialyltransferase ST3Gal-I has been proposed as a critical factor regulating the attenuation of CD8 avidity during the double-positive to CD8 single-positive progression. This hypothesis is strengthened by the fact that ST3Gal-I(-/-) animals show a profound disregulation of CD8 T cell homeostasis. In contrast to this model, however, we report in this study that ST3Gal-I deficiency had no detectable impact on CD8 noncognate binding to multimeric peptide/MHC class I ligands at any stage of thymocyte development. We also found that the susceptibility to CD8-induced cell death is not markedly influenced by ST3Gal-I deficiency. Thus, the profound effects of ST3Gal-I on CD8 T cell survival evidently do not involve a role for this enzyme in controlling CD8-class I binding.
Publication types
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Comparative Study
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Apoptosis / genetics
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Apoptosis / immunology
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CD8 Antigens / biosynthesis
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CD8 Antigens / immunology
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CD8 Antigens / metabolism*
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CD8-Positive T-Lymphocytes / cytology
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CD8-Positive T-Lymphocytes / enzymology
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CD8-Positive T-Lymphocytes / immunology
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Cell Differentiation / genetics
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Cell Differentiation / immunology*
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Histocompatibility Antigens Class I / metabolism*
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Mice, Transgenic
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Protein Binding / genetics
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Protein Binding / immunology
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Receptors, Antigen, T-Cell / metabolism*
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Sialic Acids / metabolism
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Sialyltransferases* / deficiency
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Sialyltransferases* / genetics
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Sialyltransferases* / metabolism
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Sialyltransferases* / physiology
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T-Lymphocyte Subsets / cytology*
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T-Lymphocyte Subsets / enzymology
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T-Lymphocyte Subsets / immunology
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Thymus Gland / cytology*
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Thymus Gland / enzymology
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Thymus Gland / immunology
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beta-Galactoside alpha-2,3-Sialyltransferase
Substances
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CD8 Antigens
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CD8 receptor
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Histocompatibility Antigens Class I
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Receptors, Antigen, T-Cell
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Sialic Acids
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Sialyltransferases
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beta-Galactoside alpha-2,3-Sialyltransferase