SYK expression endows human ZAP70-deficient CD8 T cells with residual TCR signaling
14.07.2015
Hauck F, Blumenthal B, Fuchs S, Lenoir C, Martin E, Speckmann C, Vraetz T, Mannhardt-Laakmann W, Lambert N, Gil M, Borte S, Audrain M, Schwarz K, Lim A, Schamel WW, Fischer A, Ehl S, Rensing-Ehl A, Picard C, Latour S.
Clin Immunol. 2015;161(2):103-109.
Mutations of signalling proteins in the immune system can be the cause of immune deficiencies. One such signalling protein studied in BIOSS is the tyrosine kinase ZAP70. Human ZAP-70 deficiency is a rare cause of severe combined immune deficiency characterized by functionally impaired CD4+ helper T cells and CD8+ cytotoxic T cell lymphopenia. Patients present with infant SCID with severe systemic infections. In this BIOSS work, we report one new ZAP70 splice site (IVS11-1G>C) mutation. We found that the oligoclonal CD8+ T cells show SYK overexpression. SYK is the second member of the ZAP-70/SYK kinase family and thus could compensate fort he loss of ZAP-70. Indeed, residual TCR signaling such as protein tyrosine phosphorylation and Ca2+-flux was demonstrated.
