T cell division and death are segregated by mutation of TCRbeta chain constant domains.
We have studied the role of the T cell receptor (TCR) beta chain transmembrane and cytoplasmic domains (betaTM/Cyto) in T cell signaling. Upon antigen stimulation, T lymphocytes expressing a TCR with mutant and betaTM and Cyto domains accumulate in large numbers and are specifically defective in undergoing activation-induced cell death (AICD). The mutant TCR poorly recruits the protein adaptor Carma-1 and is subsequently impaired in activating NF-kappaB. This signaling defect leads to a reduced expression of Fas ligand (FasL) and to a reduction in AICD. These beta chain domains are involved in discriminating cell division and apoptosis.
Laboratory of Transplantation Immunology, Department of Research, University Hospital-Basel, Hebelstrasse 20, CH-4031 Basel, Switzerland.
Emma
E
Teixeiro
Mark A
MA
Daniels
Barbara
B
Hausmann
Adam G
AG
Schrum
Dieter
D
Naeher
Immanuel
I
Luescher
Margot
M
Thome
Rafael
R
Bragado
Ed
E
Palmer
D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D017209:Apoptosis / Q000502:physiology*; D015153:Blotting, Western; D002455:Cell Division / Q000276:immunology*; D053222:Fas Ligand Protein; D005434:Flow Cytometry; D007376:Interleukin-2 / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D008969:Molecular Sequence Data; D009154:Mutation; D016328:NF-kappa B / Q000276:immunology / Q000378:metabolism; D017434:Protein Structure, Tertiary / Q000235:genetics*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*; D015375:Receptors, Interleukin-2; D015398:Signal Transduction / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; C062279:CD6 antigen; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D007376:Interleukin-2; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D016693:Receptors, Antigen, T-Cell, alpha-beta; D015375:Receptors, Interleukin-2