Abstract
Salp15 is an Ixodes scapularis salivary protein that inhibits CD4+ T cell activation through the repression of TCR ligation-triggered calcium fluxes and IL-2 production. We show in this study that Salp15 binds specifically to the CD4 coreceptor on mammalian host T cells. Salp15 specifically associates through its C-terminal residues with the outermost two extracellular domains of CD4. Upon binding to CD4, Salp15 inhibits the subsequent TCR ligation-induced T cell signaling at the earliest steps including tyrosine phosphorylation of the Src kinase Lck, downstream effector proteins, and lipid raft reorganization. These results provide a molecular basis to understanding the immunosuppressive activity of Salp15 and its specificity for CD4+ T cells.
Publication types
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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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CD4 Antigens / metabolism*
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CD4-Positive T-Lymphocytes / immunology
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CD4-Positive T-Lymphocytes / metabolism
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HeLa Cells
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Humans
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Immunosuppressive Agents / metabolism*
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Ixodes / immunology*
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Ixodes / metabolism*
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Jurkat Cells
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Ligands
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Lymphocyte Activation / immunology
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Mice
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NIH 3T3 Cells
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Peptide Fragments / immunology
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Peptide Fragments / metabolism
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Protein Binding / immunology
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Receptors, Antigen, T-Cell / antagonists & inhibitors
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Receptors, Antigen, T-Cell / physiology
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Salivary Proteins and Peptides / metabolism*
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Salivary Proteins and Peptides / physiology
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Signal Transduction / immunology
Substances
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CD4 Antigens
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Immunosuppressive Agents
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Ligands
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Peptide Fragments
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Receptors, Antigen, T-Cell
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Salivary Proteins and Peptides
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Salp15 protein, Ixodes scapularis