Most human CD3+WT31− clones with T cell receptor Cγ1 rearrangements show strong non-MHC-restricted cytotoxic activity in contrast to those with Cγ2 rearrangements

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Abstract
Clones expressing CD3 in the absence of WT31 expression were obtained by growing highly purified WT31− cells in the presence of interleukin 2 and phytohemagglutinin. Most clones showed rearrangements of T cell receptor (TcR) γ genes on both chromosomes involving all five currently identified Jγ segments. About a third of these clones had a rearranged 12 kb Kpn I band with the Jγ probe, consistent with a V9JPCγ1 rearrangement. All clones with both chromosomes rearranged to Cγ2 had low or intermediate cytotoxic activity while most of those with at least one chromosome rearranged to Cγ1 had high cytotoxic activity against both natural killer-sensitive and natural killer-resistant targets. This applied both to clones with and without the V9JPCγ1 rearrangement. Of three clones with both Cγ1 and Cγ2 rearrangements two had high activity and the other was only weakly cytotoxic. In addition, most clones showed rearrangement of TcR β genes. Some clones were capable of secreting levels of interferon-γ and tumor necrosis factor-α which were as high as those produced by CD3+4+WT31+ T cell clones. The results suggest that most human CD3+WT31− clones expressing a disulfide-linked Cγ1/δ heterodimer are capable of mediating strong non-major histocompatibility complex-restricted cytotoxicity whereas those expressing non-disulfide-linked Cγ2/δ heterodimers are not.

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