Triggering the TCR complex causes the downregulation of nonengaged receptors by a signal transduction-dependent mechanism.
Downregulation of the TCR complex is believed to be intimately tied to T cell activation, allowing serial triggering of receptors and desensitization of stimulated cells. We studied transfected and transgenic T cells expressing CD3zeta chimeras to demonstrate that ligand engagement of the TCR or chimeras causes comodulation of nonengaged receptors. Comodulation required protein tyrosine kinase activity but not trans-phosphorylation of nonengaged receptors. The TCR appears to be downregulated by at least two mechanisms. One mechanism requires direct engagement, independent of signaling. The second requires signaling and downregulates nontriggered receptors. These results shed new light on the process of TCR downregulation and indicate that the number of downregulated TCRs cannot be assumed to equal the number of engaged receptors.
San José
E
E
Centro de Biología Molecular Severo Ochoa, Universidad Autónoma de Madrid, Spain.
Borroto
A
A
Niedergang
F
F
Alcover
A
A
Alarcón
B
B
D000818:Animals; D017252:CD3 Complex / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D006801:Humans; D019169:Jurkat Cells; D008024:Ligands; D051379:Mice; D008822:Mice, Transgenic; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D015398:Signal Transduction; D014443:Tyrosine / Q000378:metabolism
D017252:CD3 Complex; C121704:CD3 antigen, zeta chain; D008024:Ligands; D011948:Receptors, Antigen, T-Cell; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases