A Revertant TCRγδ + Cell Clone Which Has Lost MHC Nonrestricted Cytotoxic Activity but Retains Redirected Killing upon Stimulation of the CD3 Receptor

Abstract

A variant nonkiller (K -) T-cell clone derived from the MHC nonrestricted killer (K +) cell line TALL-103/2 (CD3/TCRγδ +) was studied to determine whether its lytic defects were at the tumor-binding or post-binding level. The two TALL-103/2 clones were found to display similar mRNA expression of TCR/CD3 complex ϵ, ξ, γ, and δ chains, and the same mRNA and protein levels of SRC-like protein tyrosine kinase and kinase activity. However, the K - cells express much less surface CD45 RA and contain smaller intracytoplasmatic cytotoxic granules with a lower expression of the TIA-1 protein. Although the K - cells do not undergo granule exocytosis upon contact with a susceptible (K562) target, they can be triggered to degranulate and display redirected killing by activation of the CD3 receptor. Moreover, OKT3 induces PPI turnover and Ca 2+ mobilization in both the K + and K - cells, whereas K562 cells induces PPI turnover only in the K + clone. The overall data indicate that, although the K - cells have significant post-binding defects that prevent them from killing MHC nonrestricted targets, they can fully utilize their lyric machinery upon specific activation of the CD3 pathway.