Structural mutations of the T cell receptor zeta chain and its role in T cell activation.
T cell hybridomas that express zeta zeta, but not zeta eta, dimers in their T cell receptors (TCRs) produce interleukin-2 (IL-2) and undergo an inhibition of spontaneous growth when activated by antigen, antibodies to the receptor, or antibodies to Thy-1. Hybridomas without zeta and eta were reconstituted with mutated zeta chains. Cytoplasmic truncations of up to 40% of the zeta molecule reconstituted normal surface assembly of TCRs, but antigen-induced IL-2 secretion and growth inhibition were lost. In contrast, cross-linking antibodies to the TCR activated these cells. A point mutation conferred the same signaling phenotype as did the truncations and caused defective antigen-induced tyrosine kinase activation. Thus zeta allows the binding of antigen/major histocompatibility complex (MHC) to alpha beta to effect TCR signaling.
Frank
S J
SJ
Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892.
Niklinska
B B
BB
Orloff
D G
DG
Merćep
M
M
Ashwell
J D
JD
Klausner
R D
RD
D000595:Amino Acid Sequence; D000818:Animals; D003432:Cross-Linking Reagents; D004306:Dose-Response Relationship, Immunologic; D006825:Hybridomas; D007111:Immunity, Cellular; D015151:Immunoblotting; D007376:Interleukin-2 / Q000096:biosynthesis*; D008024:Ligands; D008213:Lymphocyte Activation; D008285:Major Histocompatibility Complex; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology*; D011233:Precipitin Tests; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology*; D014162:Transfection
D003432:Cross-Linking Reagents; D007376:Interleukin-2; D008024:Ligands; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell