Normal T cells express two T cell antigen receptor populations, one of which is linked to the cytoskeleton via zeta chain and displays a unique activation-dependent phosphorylation pattern.

The TCR couples antigen recognition and the transmission of activation signals. We report the expression of two TCR populations on the surface of T lymphocytes, one of which is linked to the cytoskeleton via the zeta chain. We also demonstrate that assembly of the CD3 subunits with cytoskeleton-associated zeta is necessary for their maximal localization to the cytoskeleton. The potential significance of these two receptor forms is underscored by differences observed in non-activated T cells; while detergent-soluble phosphorylated zeta appears as a 21-kDa protein, phosphorylated cytoskeleton-associated zeta appears as a 16-kDa form. This dichotomous phosphorylation pattern is rigidly maintained following activation, although each of the receptor populations undergoes different activation-dependent modifications: 1) levels of soluble phosphorylated 21-kDa zeta are enhanced, while phosphorylated 16-kDa cytoskeleton-associated zeta exhibits little change; 2) soluble non-phosphorylated 16-kDa zeta translocates to the cytoskeleton; 3) activation-dependent ubiquitinated zeta forms localize to both fractions, albeit with different kinetics. We also show that the protein tyrosine kinase Lck undergoes activation-dependent modifications and translocates to the cytoskeleton. The phosphorylation profiles of the dichotomous TCR populations in both non-activated and activated lymphocytes suggest that each population could regulate distinct cellular functions, possibly by select intermolecular associations.