CD4 DEPENDENCE OF ACTIVATION THRESHOLD AND TCR SIGNALING IN MOUSE T-LYMPHOCYTES

The effect of CD4 expression on the activation threshold of mouse T ly mphocytes has been analysed. To do this, the authors studied the respo nse to antigen and other T cell receptor (TCR) ligands in a series of CD4(-) mutants obtained from the SR.D10 clone, This non-tumour clone s pontaneously arose from the Th2 clone D10.G4.1, and characteristically shows a low threshold for antigen activation as well as reactivity to syngeneic antigen presenting cells (APC). Although SR.D10 CD4(-) muta nt cells can be stimulated bg antigen, they need higher antigen concen tration or more APC than SR.D10 or CD4 transfectants to yield optimal antigen responses, Furthermore, CD4(-) clones are not activated by syn geneic APC or by clonotypic antibodies. These effects do not correlate with changes in the expression of cell surface molecules implicated i n antigen recognition, like TCR/CD3, CD2, LFA-1, or CD45, or with lowe r p56(lck) or p59(fyn) activity in the mutant cells. Since inhibition experiments using anti-CD4 antibodies have previously shown that activ ation of the CD4(+) T cell clone D10.G4.1 by antigen or alloantigens i s largely dependent on CD4, our results indicate that activation by an tigen-plus self MHC may become CD4-independent if the activation thres hold is lowered enough, e.g. in cells like SR.D10. Expression of CD4 f urther lowers the activation threshold of the cells, allowing the dete ction of low-affinity TCR reactivities like those directed at self MHC . Moreover, bg using anti-TCR/CD3 antibodies, the authors have confirm ed the importance of CD4-associated tyrosine kinase activity in early TCR/CD3 signalling in this Th2 cell Line, as (1) upon TCR/CD3 Ligation , tyrosine phosphorylation is detected only in those CD3 chains co-pre cipitating with CD4; and (2) CD4 expression is needed for efficient ea rly tyrosine phosphorylation and detectable p56(lck)-TCR co-precipitat ion.