RESUMO
Information regarding the role of natural killer (NK) cells in the response to viruses, intracellular bacteria and parasites continues to emerge. NK cells can directly lyse infected cells, secrete cytokines and interact with dendritic cells to drive the adaptive immune response. There are a large number of activating and inhibitory receptors that govern NK cell activity. Recent studies have revealed how signals are transmitted and integrated from the variety of receptors, how particular receptors influence NK development and functional status, and how NK cells access lymph nodes and sites of infection. The potential for NK cells to exhibit specific and memory-like responses has begun to blur the 'innate' definition of NK cells.
Assuntos
Células Matadoras Naturais/imunologia , Animais , Humanos , Células Matadoras Naturais/metabolismo , Transdução de Sinais/imunologiaRESUMO
Inhibitory killer cell Ig-like receptors (KIR) signal by recruitment of the tyrosine phosphatase Src homology region 2 domain-containing phosphatase-1 to ITIM. In the present study, we show that, surprisingly, KIR lacking ITIM are able to signal and inhibit in the human NK cell line NK92, but not in mouse NK cells. Signaling by mutant KIR is weaker than the wild-type receptor, does not require the transmembrane or cytoplasmic tail of KIR, and is blocked by overexpression of a catalytically inactive Src homology region 2 domain-containing phosphatase-1 molecule. We also demonstrate that mutant KIR signaling is blocked by Abs, which disrupt the interaction between KIR and human leukocyte Ag-C or Abs, which block the interaction between Ig-like transcript 2 (ILT2) and the alpha3 domain of HLA class I molecules. Thus, although ILT2 expressed in NK92 is insufficient to signal in response to human leukocyte Ag-C alone, ILT2 can signal in a KIR-dependent manner revealing functional cooperation between receptors encoded by two distinct inhibitory receptor families.