Differential Tyrosine Phosphorylation of Zeta Chain Dimers in Mouse CD4 T Lymphocytes: Effect of Age

Antibody to the ζ chain of the CD3/TCR signal transduction complex precipitates a series of tyrosine-phosphorylated proteins that can be discriminated by electrophoresis in nonreducing polyacrylamide gels. Stimulation of resting mouse splenic CD4 T cells by cross-linking CD3 to CD4 leads to increases in tyrosine phosphorylation of five such proteins, of which three are likely to be dimeric forms of ζ as judged by behavior on two-dimensional gels. Two other phosphoproteins, of MW 38 and 55 kDa, also coprecipitate with the CD3ζ complex. The level of induced phosphorylation of each of these five stimulus-responsive phosphoproteins declines with donor age, T cells from 18-month-old mice being almost wholly nonresponsive. Resting T cells have only a single major form of tyrosine-phosphorylated ζζ. Phosphorylation of this rapidly migrating species is not influenced by activation, but is about threefold lower in resting T cells from 12- to 18-month-old mice than in cells from 6-month-old animals. Thus the phosphorylation of the CD3-ζ chain of CD4 T cells from aged mice exhibits abnormalities both in the resting state and within the first 5 min of the activation process.