A Hyperreactive Variant of a CD4+ T Cell Line Is Activated by Syngeneic Antigen Presenting Cells in the Absence of Antigen

A variant of the murine CD4+ T helper cell clone D10.G4.1 (D10) has been isolated and cloned. This line, which we have named "syngeneic-reactive D10", or SR.D10, maintains the I-Ak-restricted specificity for Conalbumin and the allogeneic specificities characteristic of D10 cells. However, it is hyperreactive to TCR-dependent and-independent stimuli, indicating a lower activation threshold than the original D10.G4.1 clone. The hyperreactivity of SR.D10 runs in parallel with the acquisition of a reactive phenotype against syngeneic antigen presenting cells (APCs). As in antigen activation, reactivity to syngeneic APCs can be inhibited by anti-TCR, anti-CD4, or anti-class II monoclonal antibodies. The role of CD4 in this phenomenon is highlighted as "syngeneic reactivity" disappears in CD4- mutants of SR.D10 and is recovered in CD4 transfectants. The expression of several cell surface molecules involved in T cell activation show qualitative and/or quantitative differences between SR/D10 and the original D10. No significant differences in quantity and activity of p56lck and p59fyn were detected between the hyperreactive and the original clone. Our results suggest that high sensitivity to activation, concomitant with expression of CD4, might allow the acquisition of an autoreactive phenotype and confirm the important contribution of coreceptors to determine the activation threshold of the cells. The characteristics of SR.D10 and the possibility of growing them in the presence of interleukins make this cell line a experimental model of great interest for analyzing activation mechanisms in T cells.