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.