Abstract
CD8 serves both as an adhesion molecule for class I MHC molecules and as a coreceptor with the TCR for T cell activation. Here we study the developmental regulation of CD8-mediated binding to noncognate peptide/MHC ligands (i.e., those not bound by the TCR). We show that CD8's ability to bind soluble class I MHC tetramers and to mediate T cell adhesion under shear flow conditions diminishes as double-positive thymocytes mature into CD8(+) T cells. Furthermore, we provide evidence that this decreased CD8 binding results from increased T cell sialylation upon T cell maturation. These data suggest that CD8's ability to interact with class I MHC is not fixed and is developmentally regulated through the T cell's glycosylation state.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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ATP Binding Cassette Transporter, Subfamily B, Member 2
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ATP-Binding Cassette Transporters / genetics
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Animals
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CD3 Complex / metabolism
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CD4-Positive T-Lymphocytes / cytology
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CD4-Positive T-Lymphocytes / immunology
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CD4-Positive T-Lymphocytes / metabolism
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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 / immunology
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CD8-Positive T-Lymphocytes / metabolism
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Cell Adhesion
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Cell Differentiation
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Cellular Senescence
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Glycosylation
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H-2 Antigens / immunology
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H-2 Antigens / metabolism*
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Histocompatibility Antigen H-2D
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Ligands
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Macromolecular Substances
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Membrane Glycoproteins / metabolism*
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Mice
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Mice, Inbred BALB C
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Mice, Inbred C57BL
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Mice, Knockout
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N-Acetylneuraminic Acid / metabolism
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Neuraminidase / pharmacology
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Ovalbumin / immunology
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Peptide Fragments / immunology
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Protein Binding
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Protein Processing, Post-Translational*
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Receptors, Antigen, T-Cell, alpha-beta / deficiency
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Receptors, Antigen, T-Cell, alpha-beta / genetics
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Rheology
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Solubility
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T-Lymphocyte Subsets / cytology*
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T-Lymphocyte Subsets / immunology
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T-Lymphocyte Subsets / metabolism
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Thymus Gland / cytology
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Thymus Gland / growth & development
Substances
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ATP Binding Cassette Transporter, Subfamily B, Member 2
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ATP-Binding Cassette Transporters
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CD3 Complex
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CD8 Antigens
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H-2 Antigens
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H-2Kb protein, mouse
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Histocompatibility Antigen H-2D
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Ligands
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Macromolecular Substances
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Membrane Glycoproteins
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Peptide Fragments
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Receptors, Antigen, T-Cell, alpha-beta
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TAP1 protein, human
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Tap1 protein, mouse
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Ovalbumin
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Neuraminidase
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N-Acetylneuraminic Acid