CD167 acts as a novel costimulatory receptor in T-cell activation.
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.
Dang
Nana
N
Department of Biochemistry and Molecular Biology, State Key Laboratory of Cancer Biology, Fourth Military Medical University, Xi'an, Shaanxi 710032, China.
Hu
Jinsong
J
Liu
Xinping
X
Li
Xia
X
Ji
Shaoping
S
Zhang
Wei
W
Su
Jin
J
Lu
Fan
F
Yang
Angang
A
Han
Hua
H
Han
Wei
W
Jin
Boquan
B
Yao
Libo
L
D015703:Antigens, CD / Q000096:biosynthesis / Q000235:genetics; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis / Q000235:genetics; D017252:CD3 Complex / Q000276:immunology; D020013:Calcium Signaling; D049109:Cell Proliferation; D002478:Cells, Cultured; D000070818:Discoidin Domain Receptors; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000096:biosynthesis / Q000235:genetics; D037181:Lectins, C-Type / Q000096:biosynthesis / Q000235:genetics; D008213:Lymphocyte Activation; D007959:Lymphocyte Culture Test, Mixed; D021962:Membrane Microdomains; D018613:Microscopy, Confocal; D010766:Phosphorylation; D021381:Protein Transport; D020239:Receptor Cross-Talk; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D011975:Receptors, Mitogen / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D000099192:CD69 Antigens
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D000070818:Discoidin Domain Receptors; D053645:Interleukin-2 Receptor alpha Subunit; D037181:Lectins, C-Type; D020794:Receptor Protein-Tyrosine Kinases; D011948:Receptors, Antigen, T-Cell; D011975:Receptors, Mitogen; D000099192:CD69 Antigens