CD2 and CD3 associate independently with CD5 and differentially regulate signaling through CD5 in Jurkat T cells

In T lymphocytes, the CD2 and CD5 glycoproteins are believed to be involved in the regulation of signals elicited by the TCR/CD3 complex. Here we show that CD2 and CD3 independently associate with CD5 in human PBMC and Jurkat cells. CD5 coprecipitates with CD2 in CD3-deficient cells and, conversely, coprecipitates with CD3 in cells devoid of CD2, In unstimulated CD2(+) CD3 (+) Jurkat cells, CD5 associates equivalently with CD2 and CD3 and is as ef ficiently phosphorylated in CD2 as in CD3 immune complexes. However, upon a ctivation the involvement of CD5 is the opposite in the CD2 and CD3 pathway s. CD5 becomes rapidly tyrosine phosphorylated after CD3 stimulation, but i s dephosphorylated upon CD2 cross-linking These opposing effects correlate with the decrease in the activity of the SH2 domain-containing protein phos phatase 1 (SHP-1) following CD3 activation vs an enhanced activity of the p hosphatase after CD2 triggering, The failure of CD5 to become phosphorylate d on tyrosine residues in the CD2 pathway has no parallel with the lack of use of zeta-chains in CD2 signaling; contrasting with comparable levels of association of CD2 or CD3 with CD5, zeta associates with CD2 only residuall y and is nevertheless slightly phosphorylated after CD2 stimulation. The mo dulation of CD5 phosphorylation may thus represent a level of regulation co ntrolled by CD2 in signal transduction mechanisms in human T lymphocytes.