CD3-negative natural killer cells express zeta TCR as part of a novel molecular complex

Natural killer (NK) cells are large granular lymphocytes capable of killing tumour cells in a non-MHC restricted manner. NK cells do not express cell-surface CD3, or any known target recognition structure analogous to the T cell antigen receptor (TCR) heterodimers (alpha beta or gamma delta). Consistent with their lack of expression of a CD3-TCR complex, NK cells do not require prior sensitization or antigen presentation by accessory cells to specifically recognize their tumour targets. Although NK cells do not express CD3-TCR, they do express CD2, the target of an alternative activation pathway which is functional in both T cells and NK cells. In T cells, this alternative activation pathway utilizes some component of the CD3-TCR complex as a transducer molecule that is required for mitogenesis. The fact that NK cells are activated by this alternative pathway suggested that they might express a related subunit of the CD3-TCR complex capable of transducing the CD2-mediated signal. Here we show that human NK cells express the zeta-chain of the TCR complex in association with additional structures not included in CD3-TCR.