A motif within the T cell receptor alpha chain constant region connecting peptide domain controls antigen responsiveness.
Mutant alphabeta TCRs were generated by replacing domains of the alpha and beta chain constant regions with homologous domains from TCR delta and gamma chains, respectively. Chimeric TCRs in which the alpha chain contains TCR delta chain sequences within the connecting peptide domain are unresponsive to alloantigens and superantigens, and have defective interactions with the CD3/zeta complex. Although these antigen-unresponsive TCRs undergo zeta chain phosphorylation upon stimulation with superantigen, they do not generate a full signal capable of producing IL-2. Mutant TCRs acquire signaling activity with a combination of superantigen and calcium ionophore, indicating a defect in calcium-mediated signaling. Finally, a conserved motif, FETDxNLN, present in the alpha chain connecting peptide domain, is disrupted in all signaling-defective TCRs. This conserved alpha chain connecting peptide motif might mediate the transfer of signals from the alphabeta heterodimer to the CD3/zeta complex.
Bäckström
B T
BT
Basel Institute for Immunology, Switzerland.
Milia
E
E
Peter
A
A
Jaureguiberry
B
B
Baldari
C T
CT
Palmer
E
E
D000595:Amino Acid Sequence; D005110:Extracellular Space / Q000276:immunology; D006801:Humans; D007424:Intracellular Fluid / Q000276:immunology; D019169:Jurkat Cells; D008213:Lymphocyte Activation / Q000187:drug effects*; D008969:Molecular Sequence Data; D010455:Peptides / Q000276:immunology* / Q000494:pharmacology*; D011487:Protein Conformation; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000235:genetics / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000502:physiology*; D016415:Sequence Alignment; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
D010455:Peptides; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta