CD167 acts as a novel costimulatory receptor in T-cell activation

J Immunother. 2009 Oct;32(8):773-84. doi: 10.1097/CJI.0b013e3181acea46.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD / biosynthesis
  • Antigens, CD / genetics
  • Antigens, Differentiation, T-Lymphocyte / biosynthesis
  • Antigens, Differentiation, T-Lymphocyte / genetics
  • CD3 Complex / immunology
  • Calcium Signaling
  • Cell Proliferation
  • Cells, Cultured
  • Discoidin Domain Receptors
  • Humans
  • Interleukin-2 Receptor alpha Subunit / biosynthesis
  • Interleukin-2 Receptor alpha Subunit / genetics
  • Lectins, C-Type / biosynthesis
  • Lectins, C-Type / genetics
  • Lymphocyte Activation
  • Lymphocyte Culture Test, Mixed
  • Membrane Microdomains
  • Microscopy, Confocal
  • Phosphorylation
  • Protein Transport
  • Receptor Cross-Talk
  • Receptor Protein-Tyrosine Kinases / genetics
  • Receptor Protein-Tyrosine Kinases / immunology
  • Receptor Protein-Tyrosine Kinases / metabolism*
  • Receptors, Antigen, T-Cell / immunology
  • Receptors, Mitogen / genetics
  • Receptors, Mitogen / immunology
  • Receptors, Mitogen / metabolism*
  • T-Lymphocyte Subsets / cytology
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism*
  • Th1 Cells / cytology
  • Th1 Cells / immunology
  • Th1 Cells / metabolism*

Substances

  • Antigens, CD
  • Antigens, Differentiation, T-Lymphocyte
  • CD3 Complex
  • CD69 antigen
  • Interleukin-2 Receptor alpha Subunit
  • Lectins, C-Type
  • Receptors, Antigen, T-Cell
  • Receptors, Mitogen
  • Discoidin Domain Receptors
  • Receptor Protein-Tyrosine Kinases