RT info:eu-repo/semantics/article T1 Differential role of SLP-76 domains in T cell development and function A1 Kumar, Lalit A1 Pivniouk, Vadim A1 Fuente García, Miguel Ángel de la A1 Laouini, Dhafer A1 Geha, Raif S. K1 Biología molecular AB The adapter SLP-76 is essential for thymocyte development. SLP-76−/− mice were reconstituted with SLP-76 deletion mutant transgenes to examine the role of SLP-76 domains in T cell development and function. The N-terminal domain deletion mutant completely failed to restore thymocyte development. Mice reconstituted with Gads-binding site and SH2 domain deletion mutants had decreased thymic cellularity, impaired transition from double to single positive thymocytes, and decreased numbers of mature T cells in the spleen. Calcium mobilization and extracellular signal-regulated protein kinase activation were decreased in the Gads-binding site mutant but almost normal in the SH2 domain mutant. T cells from both mutants failed to proliferate following T cell antigen receptor ligation. Nevertheless, both mutants mounted partial cutaneous hypersensitivity responses and normal T cell dependent IgG1 antibody responses. These results indicate differential roles for SLP-76 domains in T cell development, proliferation and effector functions. SN 1091-6490 YR 2002 FD 2002 LK http://uvadoc.uva.es/handle/10324/10153 UL http://uvadoc.uva.es/handle/10324/10153 LA eng NO Proceedings of the National Academy of Sciences of the United States of America, 2002, vol. 99, n. 2. p. 884-889 NO Producción Científica DS UVaDOC RD 22-dic-2024