Topic: Inborn errors of immunity: A Novel Role for Magnesium in Regulation of T cell

Speaker: Dr. Chrysi Kanellopoulou

                Research Fellow, NIAID, National Institutes of Health

Time: 14:00-15:30, April 12th (Wed.), 2017

Location: D326, Medical Science Building

Host: Dr. Wanli Liu

Abstract:

We have previously described a human primary immunodeficiency due to mutations in the magnesium transporter MAGT1, named XMEN disease (X-linked Magnesium defect with Epstein-Barr infection and Neoplasia). Loss of MAGT1 results in impaired T cell receptor signaling. Previous analyses suggested that proximal TCR signaling events were unaffected in XMEN patients but PLCγ1 phosphorylation was delayed. We have further characterized the TCR activation defect in MAGT1 deficient cells and found that the primary cause is the impaired activity of Interleukin-2 inducible T cell kinase (ITK): ITK is phosphorylated normally by LCK and recruited to immunological synapse but fails to phosphorylate downstream targets efficiently. In vitro kinase assays show that ITK activity is tightly regulated by magnesium and significantly enhanced in physiologic range of magnesium concentrations. We propose a model in which magnesium is a major regulator of ITK and discuss the possibility that this is a common feature of kinases.