Abstract
CD8 engagement is believed to be a critical event in the activation of naive T cells. In this communication, we address the effects of peptide-MHC (pMHC)/TCR affinity on the necessity of CD8 engagement in T cell activation of primary naive cells. Using two peptides with different measured avidities for the same pMHC-TCR complex, we compared biochemical affinity of pMHC/TCR and the cell surface binding avidity of pMHC/TCR with and without CD8 engagement. We compared early signaling events and later functional activity of naive T cells in the same manner. Although early signaling events are altered, we find that high-affinity pMHC/TCR interactions can overcome the need for CD8 engagement for proliferation and CTL function. An integrated signal over time allows T cell activation with a high-affinity ligand in the absence of CD8 engagement.
Publication types
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Comparative Study
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Antigens, Viral / immunology
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Aspartic Acid / genetics
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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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COS Cells
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Chlorocebus aethiops
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Cytokines / metabolism
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Cytotoxicity, Immunologic
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Glycoproteins / immunology
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H-2 Antigens / genetics
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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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Lymphocyte Activation / genetics
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Lymphocytic choriomeningitis virus / immunology
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Lysine / genetics
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Membrane Microdomains / genetics
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Membrane Microdomains / immunology
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Membrane Microdomains / metabolism
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Mice
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Mice, Inbred C57BL
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Mice, Transgenic
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Mutagenesis, Site-Directed
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Peptide Fragments / genetics
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Peptide Fragments / immunology*
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Peptide Fragments / metabolism*
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Protein Binding / genetics
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Protein Binding / immunology
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Protein Structure, Tertiary / genetics
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Receptor Cross-Talk / immunology*
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Receptors, Antigen, T-Cell / metabolism*
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Receptors, Antigen, T-Cell / physiology
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Signal Transduction / genetics
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Signal Transduction / immunology
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Viral Proteins / immunology
Substances
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Antigens, Viral
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CD8 Antigens
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Cytokines
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Glycoproteins
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H-2 Antigens
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Histocompatibility Antigen H-2D
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Ligands
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Peptide Fragments
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Receptors, Antigen, T-Cell
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Viral Proteins
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glycoprotein peptide 33-41, Lymphocytic choriomeningitis virus
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Aspartic Acid
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Lysine