EphB6-null mutation results in compromised T cell function
Hongyu Luo, … , Johanne Tremblay, Jiangping Wu
Hongyu Luo, … , Johanne Tremblay, Jiangping Wu
Published December 15, 2004
Citation Information: J Clin Invest. 2004;114(12):1762-1773. https://doi.org/10.1172/JCI21846.
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Article Immunology

EphB6-null mutation results in compromised T cell function

Abstract

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 PLCγ1 with SLP-76, and p44/42 MAPK activation were diminished. Thus, we have shown that EphB6 is pivotal in T cell function.

Authors

Hongyu Luo, Guang Yu, Johanne Tremblay, Jiangping Wu

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Figure 6

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EphB6 cocapped with TCR and rafts upon TCR stimulation. Capping of thymo...
EphB6 cocapped with TCR and rafts upon TCR stimulation. Capping of thymocyte TCR (A–C; stained with biotinylated anti-CD3 and biotinylated anti-CD4 followed by streptavidin–Alexa Fluor 594 in red), EphB6 (A, B, and D; stained with goat anti–mouse EphB6 followed by Alexa Fluor 488–conjugated donkey anti-goat IgG in green), and rafts (D; stained by Alexa Fluor 594–conjugated cholera toxin in red) was assessed by confocal microscopy. Thymocyte surface CD45 (C; stained with FITC-conjugated anti-CD45) was used as a control. “Resting” indicates thymocytes without stimulation; “activated” indicates thymocytes cross-linked with anti-CD3 and anti-CD4 at 37–C for 2 minutes. All experiments were performed at least 3 times and were reproducible; representative results are shown.