INFLUENCE ON CD8 OF TCR CD3-GENERATED SIGNALS IN CTL CLONES AND CTL PRECURSOR CELLS/

Alloreactive CTL clones and naive CTL precursor cells (CTLp) from TCR- transgenic mice were analyzed for their response in total and in TCR-a ssociated kinase activation upon stimulation with the relevant class I allo-APCs, The responses were found to be stronger and more sustained for the CTL clone and CTLp expressing a TCR previously characterized as CD8 coreceptor independent than for the CTL clone and CTLp expressi ng a TCR characterized as CD8 dependent, Unexpectedly, it was found th at also in response to CD3 engagement, total and TCR-associated kinase activation were stronger and more sustained in the CTL clone and CTLp expressing the CD8-independent TCR, In both types of CTL clones, p56( kk) was found associated with the TCR complex, and CD3 components were found associated with CD8 before CD3 engagement, Upon CD3 engagement, ZAP-70 was also found associated with the TCR complex and the kinase activity (p56(kk)) associated with CD8 increased, This increase was mo re pronounced for the CD8-independent than for the CD8-dependent clone . An increased association of CD3 zeta with CD8 was also detected afte r CD3 engagement for each clone, These data indicate that signals resu lting from exclusive CD3 engagement can influence CD8 molecular associ ations and activate CD8-bound p56(kk), They further suggest that clona l differences exist that influence the efficiency of signaling upon bi nding of the same CD3 ligand. The observation that this property was s hared between independently derived CTL clone and CTLp expressing the same TCR suggests that it may be acquired during repertoire selection.