T-CELL RECEPTOR JUNCTIONAL REGIONS OF V-GAMMA-9+ V-DELTA-2+ T-CELL CLONES IN RELATION TO NON-MHC RESTRICTED CYTOTOXIC ACTIVITY/

Human gammadelta T cell clones having Vgamma9JP and Vdelta2DJ1 T cell receptor (TCR) gene rearrangements were isolated from an individual do nor and tested for non-MHC restricted cytotoxicity against the B lymph oblastoid cell line, BSM. Most clones were highly cytotoxic but 3/9 cl ones had very low activity, comparable to that of CD4+ alphabeta T cel l clones. Although there was a tendency for clones with low cytotoxic function to produce high levels of interferon-gamma and tumor necrosis factor-alpha, this correlation was not complete. TCR gamma and delta junctional sequences were obtained and were found to be different for all clones. There were no consistent structural differences between ga mmadelta TCRs of cytotoxic and non-cytotoxic clones, but gamma or delt a junctional regions of all three non-cytotoxic clones had unusual fea tures. One clone had a particularly short gamma chain junctional seque nce, one had a short delta chain junctional sequence and the third clo ne was the only one of the panel which failed to utilise the Ddelta3 s egment. If the gammadelta TCR is involved in target cell recognition i n this model of non-MHC restricted killing, such variations in recepto r structure may be sufficient to inhibit recognition and thereby reduc e the cytotoxic capacity of a minority of Vgamma9+/Vdelta2+ clones. Al so, a panel of gammadelta T cell clones expressing Vgamma8/Vdelta3 iso lated from a different donor, were all highly cytotoxic against BSM, i ndicating that these target cells can be recognised by effector cells expressing a TCR other than the Vgamma9/Vdelta2 receptor. The possible influence of other cell surface molecules on non-MHC restricted cytot oxic function is discussed.