A HYPERREACTIVE VARIANT OF A CD4(-CELL LINE IS ACTIVATED BY SYNGENEICANTIGEN-PRESENTING CELLS IN THE ABSENCE OF ANTIGEN() T)

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-r eactive D10'', or SR.D10, maintains the I-A(k)-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 a cquisition of a reactive phenotype against syngeneic antigen presentin g cells (APCs). As in antigen activation, reactivity to syngeneic APCs can be inhibited by anti-TCR, anti-CD4, or anti-class II monoclonal a ntibodies, The role of CD4 in this phenomenon is highlighted as ''syng eneic reactivity'' disappears in CD4(-) mutants of SR.D10 and is recov ered in CD4 transfectants. The expression of several cell surface mole cules involved in T cell activation show qualitative and/or quantitati ve differences between SR.D10 and the original D10. No significant dif ferences in quantity and activity of p56(lck) and p59(fyn) were detect ed between the hyperreactive and the original clone. Our results sugge st that high sensitivity to activation, concomitant with expression of CD4, might allow the acquisition of an autoreactive phenotype and con firm the important contribution of coreceptors to determine the activa tion threshold of the cells, The characteristics of SR.D10 and the pos sibility of growing them in the presence of interleukins make this cel l line a experimental model of great interest for analyzing activation mechanisms in T cells. (C) 1995 Academic Press, Inc.