T cell receptor alpha-chain tail is required for protein kinase C-mediated down-regulation, but not for signaling.
Antigen stimulation through the T cell receptor (TCR) induces phosphorylation of the associated CD3 gamma delta epsilon- and zeta-chain cytoplasmic tails. These events lead to the induction of the intracellular signaling pathways with concomitant receptor down-regulation. The TCR is down-regulated from the cell surface by the activation of protein kinase, C (PKC) and subsequent serine phosphorylation of the CD3 gamma-chain. We report here that the TCR alpha-chain cytoplasmic tail is also necessary for PKC-mediated internalization of the TCR complex. The requirement for the TCR alpha-chain cytoplasmic tail is specific for internalization of the TCR complex, since down-regulation of CD4 is still intact in hybridoma cells expressing a tailless TCR alpha-chain. The absence of TCR internalization directly correlates with defective PKC-mediated phosphorylation of the CD3 gamma-chain. Despite deficient PKC-mediated TCR down-regulation, the tailless alpha beta TCR still transduces antigenic signals resulting in the production of interleukin-2. Although the TCR tails are not obviously required for signal transduction, the TCR alpha-tail may serve as a targeting domain for PKC-mediated down-regulation of the TCR complex.
Bäckström
B T
BT
Basel Institute for Immunology, Switzerland. backstrom@bii.ch
Rubin
B
B
Peter
A
A
Tiefenthaler
G
G
Palmer
E
E
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D003593:Cytoplasm / Q000737:chemistry / Q000201:enzymology / Q000276:immunology; D015536:Down-Regulation / Q000276:immunology*; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D011493:Protein Kinase C / Q000502:physiology*; D017434:Protein Structure, Tertiary; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000096:biosynthesis / Q000737:chemistry; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000737:chemistry / Q000502:physiology*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology*
D017260:Receptor-CD3 Complex, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D011493:Protein Kinase C