EphB6-null mutation results in compromised T cell function

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.
Journal of Clinical Investigation (Impact Factor: 13.22). 01/2005; 114(12):1762-73. DOI: 10.1172/JCI21846
Source: PubMed


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.

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    • "Cytosolic and nuclear extracts of these cells were prepared with NE-PER nuclear and cytoplasmic extraction kit (Pierce Biotechnology, Rockford , IL) according to the manufacturer's instructions. Various proteins in these extracts were detected by immunoblotting, as described previously [15]. The following antibodies (Abs) were deployed for immunoblotting: rabbit Abs against histone H3 and Ran (Santa Cruz Biotechnology, Santa Cruz, CA); rabbit Abs against c-Jun, c-Fos and monoclonal antibody (mAb) against b-actin (Cell Signalling, Beverly, MA). "
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    FEBS letters 10/2010; 584(22):4623-6. DOI:10.1016/j.febslet.2010.10.030 · 3.17 Impact Factor
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    • "EphA10 is a recently described Eph receptor in humans [25] and there is not previous work on its functional roles. By contrast, EphB6 has been only associated with T lymphocytes [26], in which it seems to be involved in cell signalling [8] [19] [20] [27]. Thus, although not previously described in B lymphocytes, this molecule could be also involved in B-cell activation and, as it will be later discussed, Eph B6 emerges from the current results as a good molecular marker for CLL prognosis. "
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    • "EphB receptors have been demonstrated to regulate T cell responses and responses mediated by the T cell receptor. Of the EphB receptors, evidence is strongest to support a role of the EphB6 receptor in immune regulation, including a decreased immune response detected in EphB6 knockout mice 51. EphA receptors and their ligands are expressed by T cells and are thought to regulate signaling through the T cell receptor 52, 53. "
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