EphrinB1 is essential in T-cell-T-cell co-operation during T-cell activation.
Eph kinases are the largest family of receptor tyrosine kinases, and their ligands are ephrins (EFNs), which are also cell surface molecules. We have very limited knowledge about the expression and function of these kinases and their ligands in the immune system. In this study we investigated the effect of EFNB1 on mouse T-cells. EFNB1 and the Eph kinases it interacts with (collectively called EFNB1 receptors (EFNB1R)) were expressed on T-cells, B cells, and monocytes/macrophages. Some T-cells were double positive for EFNB1 and EFBB1R. Solid phase EFNB1 in the presence of suboptimal TCR ligation augmented T-cell responses in terms interferon-gamma secretion, proliferation, and cytotoxic T lymphocyte activity but not interleukin-2 production. After T-cell receptor (TCR) ligation, EFNB1R congregated to TCR caps, and then both of them translocated to raft caps. This provides a morphological basis for EFNB1R to enhance TCR signaling. Further downstream of the signaling pathway, EFNB1R stimulation led to increased LAT (linker for activation of T-cells) phosphorylation and p44/42 and p38 MAPK activation. Similar to CD28 costimulation, EFNB1R costimulation was insensitive to cyclosporin A inhibition. On the other hand, unlike the former, EFNB1R costimulation failed to activate Akt, which is essential in triggering interleukin-2 production. Our study suggests that EFNB1 is pivotal in T-cell-T-cell costimulation and in reducing T-cell response threshold to antigen stimulation.
Yu
Guang
G
Laboratory of Immunology, Notre-Dame Hospital, Centre Hospitalier de l'Universite de Montreal, Pavilion DeSève, 1560 Sherbrooke Street East, Montreal H2L 4M1, Quebec, Canada.
Luo
Hongyu
H
Wu
Yulian
Y
Wu
Jiangping
J
D000818:Animals; D000941:Antigens / Q000737:chemistry; D018106:CD28 Antigens / Q000096:biosynthesis; D017252:CD3 Complex / Q000096:biosynthesis; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D002450:Cell Communication; D049109:Cell Proliferation; D003432:Cross-Linking Reagents / Q000494:pharmacology; D016572:Cyclosporine / Q000037:antagonists & inhibitors / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D036387:Ephrin-B1 / Q000378:metabolism / Q000502:physiology*; D005434:Flow Cytometry; D015151:Immunoblotting; D017403:In Situ Hybridization; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D007962:Leukocytes / Q000378:metabolism; D008213:Lymphocyte Activation; D008222:Lymphokines / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D009000:Monocytes / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000378:metabolism*; D013936:Thymidine / Q000737:chemistry; D013997:Time Factors; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D000941:Antigens; D018106:CD28 Antigens; D017252:CD3 Complex; D003432:Cross-Linking Reagents; D016207:Cytokines; D018076:DNA, Complementary; D036387:Ephrin-B1; D007376:Interleukin-2; D008222:Lymphokines; D011948:Receptors, Antigen, T-Cell; D007371:Interferon-gamma; D016572:Cyclosporine; D048051:p38 Mitogen-Activated Protein Kinases; D013936:Thymidine