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The current transplant immunology dogma defends that allograft rejection is initiated by recipient's adaptive immune system. In this prevalent model, innate immune cells in general, and natural killer (NK) cells in particular, are merely considered as downstream effectors which participate in the destruction of the graft only upon recruitment by adaptive effectors: alloreactive T cells or donor‐specific antibodies (DSA). Challenging this vision, recent data demonstrated that recipients' NK cells are capable of a form of allorecognition because they can sense the absence of self HLA class I molecules on the surface of graft endothelial cells. Missing‐self triggers mTORC1‐dependent activation of NK cells, which in turn promote the development of graft microvascular inflammation and detrimentally impact graft survival. The fact that some patients develop chronic vascular rejection in absence of DSA or genetically‐predicted missing self suggests that other molecular mechanisms could underly NK cell allorecognition. This review provides an overview of these proven and putative molecular mechanisms and discusses future research directions in this emerging field in organ transplant immunology. [ABSTRACT FROM AUTHOR]

Natural killer (NK) cells are potent immune effector cells that can respond to infection and cancer, as well as allowing maternal adaptation to pregnancy. In response to malignant transformation or pathogenic invasion, NK cells can secrete cytokine and may be directly cytolytic, as well as exerting effects indirectly through other cells of the immune system. To recognize and respond to inflamed or infected tissues, NK cells express a variety of activating and inhibitory receptors including NKG2D, Ly49 or KIR, CD94-NKG2 heterodimers and natural cytotoxicity receptors, as well as co-stimulatory receptors. These receptors recognize cellular stress ligands as well as major histocompatibility complex class I and related molecules, which can lead to NK cell responses. Importantly, NK cells must remain tolerant of healthy tissue, and some of these receptors can also prevent activation of NK cells. In this review, we describe the expression of prominent NK cell receptors, as well as expression of their ligands and their role in immune responses. In addition, we describe the main signaling pathways used by NK cell receptors. Although we now appreciate that NK cell biology is more complicated than first thought, there are still facets of their biology that remain unclear. These will be highlighted and discussed in this review. [ABSTRACT FROM AUTHOR]