EphB6-null mutation results in compromised T cell function.
So far, there is very limited knowledge about the role of Eph kinases, the largest family of receptor tyrosine kinases, in the immune system. Here, using EphB6(-/-) mice, we demonstrated that in vitro and in vivo T cell responses such as lymphokine secretion, proliferation, and the development of delayed-type skin hypersensitivity and experimental autoimmune encephalitis in EphB6(-/-) mice were compromised. On the other hand, humoral immune responses, such as serum levels of different Ig isotypes and IgG response to tetanus toxoid, were normal in these mice. Mechanistically, we showed that EphB6 migrated to the aggregated TCRs and rafts after TCR activation. Further downstream, in the absence of EphB6, ZAP-70 activation, LAT phosphorylation, the association of PLCgamma1 with SLP-76, and p44/42 MAPK activation were diminished. Thus, we have shown that EphB6 is pivotal in T cell function.
Luo
Hongyu
H
Laboratory of Immunology, Centre de Recherché, Notre Dame Hospital, Centre Hospitalier de l'Université de Montréal, Pavilion DeSève, 1560 Sherbrooke Street East, Montréal, Quebec H2L 4M1, Canada.
Yu
Guang
G
Tremblay
Johanne
J
Wu
Jiangping
J
D000818:Animals; D000941:Antigens / Q000378:metabolism; D015703:Antigens, CD / Q000096:biosynthesis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis; D019921:Biotinylation; D018106:CD28 Antigens / Q000096:biosynthesis; D017252:CD3 Complex / Q000096:biosynthesis; D049109:Cell Proliferation; D016207:Cytokines / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D005091:Exons; D005260:Female; D005434:Flow Cytometry; D017353:Gene Deletion; D049452:Green Fluorescent Proteins / Q000378:metabolism; D017578:Immunoglobulin Class Switching; D037181:Lectins, C-Type; D007962:Leukocytes / Q000378:metabolism; D008024:Ligands; D008214:Lymphocytes / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D008957:Models, Genetic; D009154:Mutation; D016133:Polymerase Chain Reaction; D036261:Receptor, EphB6 / Q000235:genetics* / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis; D015398:Signal Transduction; D013154:Spleen / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism*; D013950:Thymus Gland / Q000378:metabolism; D013997:Time Factors; D000099192:CD69 Antigens
D000941:Antigens; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D018106:CD28 Antigens; D017252:CD3 Complex; D016207:Cytokines; D049452:Green Fluorescent Proteins; D037181:Lectins, C-Type; D008024:Ligands; D036261:Receptor, EphB6; D011948:Receptors, Antigen, T-Cell; D015375:Receptors, Interleukin-2; D000099192:CD69 Antigens