Natural killer clones derived from fetal (25 wk) blood. Probing the human T cell receptor with WT31 monoclonal antibody

We have conducted a phenotypic and functional analysis of 19 cloned cell lines generated after allogeneic stimulation of circulating lymphocytes from a normal human fetus aged 25 wk. Using a limited series of mAbs (Anti-T3, WT31, T4, T8, and NKH1A), cloned cells were found to fall in three groups. Three clones have a conventional "inducer" phenotype. Three clones have a phenotype (T3+, WT31+, T8+, and NKH1A+) similar to that of certain NK active mature T lymphocytes present in adult peripheral blood. In contrast, 13 cell lines display surface characteristics that have not been described previously. Indeed, they express T3 proteins but not the WT31 determinant. In light of previous studies, these results show that WT31 mAb is a unique reagent directed at an invariant epitope of the human T cell receptor that is not present on all circulating T3+ fetal lymphocytes. Functionally the T3+, WT31+, and NKH1A+ clones were found to kill immunizing LAZ 388 cells, as well as K562, while T3+, WT31- and NKH1A+ clones display NK-like function exclusively. Moreover, only WT31+ lymphocytes present in the cell line used for cloning experiments have the capacity to recognize alloantigen-bearing cells. Together, these data suggest that expression of WT31 may be necessary for recognition of alloantigens, while NK reactions mediated by T3+ lymphocytes are WT31-independent.