Structure/function of human killer cell immunoglobulin-like receptors: Lessons from polymorphisms, evolution, crystal structures and mutations

Institute for Cancer Research, Fox Chase Cancer Center, Philadelphia, PA 19111, USA.
Immunology (Impact Factor: 3.74). 03/2011; 132(3):315-25. DOI: 10.1111/j.1365-2567.2010.03398.x
Source: PubMed

ABSTRACT Stimulation or tolerance of natural killer (NK) cells is achieved through a cross-talk of signals derived from cell surface activating and inhibitory receptors. Killer cell immunoglobulin-like receptors (KIR) are a family of highly polymorphic activating and inhibitory receptors that serve as key regulators of human NK cell function. Distinct structural domains in different KIR family members determine function by providing docking sites for ligands or signalling proteins. Here, we review a growing body of literature that has identified important structural elements on KIR that contribute to function through studies of engineered mutants, natural polymorphic sequence variants, crystal structure data and the conservation of protein sequences throughout primate evolution. Extensive natural polymorphism is associated with both human KIR and their ligands, MHC class I (HLA-A, -B and -C) molecules, and numerous studies have demonstrated associations between inheritance of certain combinations of KIR and HLA genes and susceptibility to several diseases, including viral infections, autoimmune disorders and cancers. In addition, certain KIR/HLA combinations can influence pregnancy and the outcome of haematopoietic stem cell transplantation. In view of the significant regulatory influences of KIR on immune function and human health, it is essential to fully understand the impacts of these polymorphic sequence variations on ligand recognition, expression and function of the receptor.

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Available from: Kerry S Campbell, Aug 09, 2015
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    • "These receptors regulate immunity and modulate cytotoxicity to tumor and virus-infected cells but have not been shown to directly trigger a cytolytic pathway (Baratin et al., 2005; Sivori et al., 2004). By contrast, the known NK activating receptors that recognize tumor or virus-infected cells consist of four families, including natural killer group 2 (NKG2), natural cytotoxicity receptors (NCR), the noninhibitory killer inhibitor receptors (KIR), and the signaling lymphocyte activation molecule (SLAM) family (Biassoni, 2008; Campbell and Purdy, 2011; Cannons et al., 2011). However, despite their known functions in cytotoxicity of tumor and virus-infected cells, none of these receptors have been implicated in recognition of fungi. "
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    Cell host & microbe 10/2013; 14(4):387-97. DOI:10.1016/j.chom.2013.09.007 · 12.19 Impact Factor
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    Archivum Immunologiae et Therapiae Experimentalis 04/2013; 61(4). DOI:10.1007/s00005-013-0225-2 · 2.82 Impact Factor
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    • "Table 1 | Ligands of KIR molecules (based on Kusnierczyk, 2006; Graef et al., 2009; Campbell and Purdy, 2011; Parham et al., 2012b "
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