Heterogeneous binding and killing behaviour of human γ/δ-TCR⁺ lymphokine-activated killer cells against K562 and Daudi cells

Abstract

Effector-target conjugates, formed by coincubation of lymphokine-activated killer (LAK) cells with either K562 or Daudi cells, were separated from single cells by Percoll sedimentation. The occurrence of various CD molecules (CD3, CD56, CD57, CD16, γ/δ-TCR) was compared in both fractions. Only LAK cells expressing the γ/δ T cell receptor (TCR) were found in a significantly increased percentage in fractions containing conjugates indicating that γ/δ-TCR⁺ LAK cells were preferably bound to target cells at the time of separation. In order to determine whether γ/δ-TCR⁺ LAK cells also show a preferred killing activity against the targets, cultures enriched with or depleted of γ/δ-TCR⁺ cells were established. Against K562 cells, γ/δ-TCR⁺-enriched cultures showed a greatly reduced killing activity compared to LAK bulk cultures or cultures depleted of γ/δ-TCR⁺ cells. Using Daudi cells as targets the enriched fraction revealed a slightly increased killing activity compared to bulk cultures or depleted fractions. Preincubation of γ/δ-TCR⁺ LAK cells with anti-γ/δ or anti-CD3 mAb resulted in a distinct increase of the killing activity against K562 cells, but in only a slightly enhanced activity against Daudi cells. It is postulated that γ/δ-TCR⁺ LAK cells use the same adhesion mechanism for both targets but that only Daudi cells express a specific ligand for the γ/δ-TCR. Occupation of the γ/δ-TCR/CD3 complex by mAb, however, seems to substitute for the absent epitope on K562 cells by eliciting stimulatory signals in γ/δ-TCR⁺ LAK cells which, in combination with the binding stimulus, trigger cytolytic activity.