Strategies of Natural Killer (NK) Cell Recognition and Their Roles in Tumor Immunosurveillance

Abstract

Natural Killer cells (NK cells) represent an interesting epistemological example in Immunology. First considered as “background noise” in T-cell cytolytic assays, Natural Killer (NK) cells were characterized more than 30 years ago as cytotoxic effectors of the innate immune system (Kiessling et al. 1975). Later, NK cells were recognized as a peculiar type of large granular lymphocytes that are widespread throughout the body (Lanier et al. 1986), being present in both lymphoid organs and non-lymphoid peripheral tissues (Cooper et al. 2004; Ferlazzo and Munz 2004). Their specificity for a variety of tumor cells, virus-infected cells or allogeneic cells along with their lack of antigen-specific receptors, have puzzled immunologists for many years. Since this time, a series of discoveries have shed light on the mechanisms of NK cell effector function and have simultaneously broadened our views on immune detection strategies (Carayannopoulos and Yokoyama 2004; Lanier 2005; Moretta et al. 2002; Stewart et al. 2006; Vivier and Biron 2002). Such discoveries include “missing-self recognition” (via major histocompatibility complex [MHC] class I) (Kärre et al. 1986), the identification of inhibitory cell surface receptors that modulate NK cell activation (via Immunoreceptor Tyrosine-based Inhibition Motifs: ITIM) (Vély and Vivier 1997) or the “stress-induced self recognition” (via NKG2D) (Raulet 2003) (Fig. 1). The involvement of NK cells in the control of viral and parasitic infections, in auto-immunity, in reproduction as well as in the clinical outcome of hematopoietic transplants has been reviewed recently (Carayannopoulos and Yokoyama 2004; Johansson et al. 2005; Korbel et al. 2004; Lodoen and Lanier 2005; Orange and Ballas 2006; Parham 2005; Ruggeri et al. 2005; Zhang et al. 2005).