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 ce ll activation, allowing serial triggering of receptors and desensitization of stimulated cells. We studied transfected and transgenic T cells expressi ng CD3 xi chimeras to demonstrate that ligand engagement of the TCR or chim eras causes comodulation of nonengaged receptors. Comodulation required pro tein tyrosine kinase activity but not trans-phosphorylation of nonengaged r eceptors. The TCR appears to be downregulated by at least two mechanisms. O ne mechanism requires direct engagement, independent of signaling. The seco nd requires signaling and downregulates nontriggered receptors. These resul ts shed new light on the process of TCR downregulation and indicate that th e number of downregulated TCRs cannot be assumed to equal the number of eng aged receptors.