Differential role of SLP-76 domains in T cell development and function.
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.
Kumar
Lalit
L
Division of Immunology, Children's Hospital, Boston, MA 02115, USA.
Pivniouk
Vadim
V
de la Fuente
Miguel A
MA
Laouini
Dhafer
D
Geha
Raif S
RS
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D001665:Binding Sites / Q000235:genetics; D002118:Calcium / Q000378:metabolism; D002454:Cell Differentiation; D002455:Cell Division; D007527:Isoenzymes / Q000378:metabolism; D037181:Lectins, C-Type; D008213:Lymphocyte Activation; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009154:Mutation; D010047:Ovalbumin / Q000276:immunology; D051966:Phospholipase C gamma; D010750:Phosphoproteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D017434:Protein Structure, Tertiary; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D017384:Sequence Deletion; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D010738:Type C Phospholipases / Q000378:metabolism; D018909:src Homology Domains; D000099192:CD69 Antigens
D048868:Adaptor Proteins, Signal Transducing; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D002118:Calcium; D007527:Isoenzymes; D037181:Lectins, C-Type; D020928:Mitogen-Activated Protein Kinases; D010047:Ovalbumin; D051966:Phospholipase C gamma; D010750:Phosphoproteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D015375:Receptors, Interleukin-2; D010738:Type C Phospholipases; D000099192:CD69 Antigens; C092947:SLP-76 signal Transducing adaptor proteins