Abstract
Optimal T-cell activation requires both an antigen-specific and a costimulatory signal. CD167 is a tyrosine kinase receptor for native type I collagen, its physiologic functions include matrix homeostasis and cell growth, adhesion, branching, and migration, but the specific role of CD167 in T cells has not yet been characterized. In this study, we found that CD167 expression on T cells was up-regulated after activation. Cooperation of CD167 engagement with suboptimal TCR/CD3 signals induced T-cell proliferation, enhanced expression of activation markers such as CD25 and CD69, elevated intracellular calcium mobilization and tyrosine phosphorylation, and introduced a bias toward a TH1/Tc1 immune response. Cooperation of CD167 engagement also enhanced mixed lymphocyte responses to alloantigens. Moreover, CD167 rapidly localized to the aggregated lipid rafts upon T-cell activation, this provided a molecular base for the signaling machinery of CD167. Together these findings, we demonstrate for the first time that CD167 could serve as a novel costimulatory receptor for T-cell activation.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antigens, CD / biosynthesis
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Antigens, CD / genetics
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Antigens, Differentiation, T-Lymphocyte / biosynthesis
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Antigens, Differentiation, T-Lymphocyte / genetics
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CD3 Complex / immunology
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Calcium Signaling
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Cell Proliferation
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Cells, Cultured
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Discoidin Domain Receptors
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Humans
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Interleukin-2 Receptor alpha Subunit / biosynthesis
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Interleukin-2 Receptor alpha Subunit / genetics
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Lectins, C-Type / biosynthesis
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Lectins, C-Type / genetics
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Lymphocyte Activation
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Lymphocyte Culture Test, Mixed
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Membrane Microdomains
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Microscopy, Confocal
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Phosphorylation
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Protein Transport
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Receptor Cross-Talk
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Receptor Protein-Tyrosine Kinases / genetics
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Receptor Protein-Tyrosine Kinases / immunology
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Receptor Protein-Tyrosine Kinases / metabolism*
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Receptors, Antigen, T-Cell / immunology
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Receptors, Mitogen / genetics
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Receptors, Mitogen / immunology
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Receptors, Mitogen / metabolism*
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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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Th1 Cells / cytology
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Th1 Cells / immunology
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Th1 Cells / metabolism*
Substances
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Antigens, CD
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Antigens, Differentiation, T-Lymphocyte
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CD3 Complex
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CD69 antigen
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Interleukin-2 Receptor alpha Subunit
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Lectins, C-Type
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Receptors, Antigen, T-Cell
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Receptors, Mitogen
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Discoidin Domain Receptors
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Receptor Protein-Tyrosine Kinases