A bird's eye view of NK cell receptor interactions with their MHC class I ligands.
The surveillance of target cells by natural killer (NK) cells utilizes an ensemble of inhibitory and activating receptors, many of which interact with major histocompatibility complex (MHC) class I molecules. NK cell recognition of MHC class I proteins is important developmentally for the acquisition of full NK cell effector capacity and during target cell recognition, where the engagement of inhibitory receptors and MHC class I molecules attenuates NK cell activation. Human NK cells have evolved two broad strategies for recognition of human leukocyte antigen (HLA) class I molecules: (i) direct recognition of polymorphic classical HLA class I proteins by diverse receptor families such as the killer cell immunoglobulin-like receptors (KIRs), and (ii) indirect recognition of conserved sets of HLA class I-derived peptides displayed on the non-classical HLA-E for recognition by CD94-NKG2 receptors. In this review, we assess the structural basis for the interaction between these NK receptors and their HLA class I ligands and, using the suite of published KIR and CD94-NKG2 ternary complexes, highlight the features that allow NK cells to orchestrate the recognition of a range of different HLA class I proteins.
Department of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia.
Philippa M
PM
Saunders
Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Clayton, VIC, Australia.|ARC Centre of Excellence in Advanced Molecular Imaging, Monash University, Clayton, VIC, Australia.
Julian P
JP
Vivian
Department of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia.
Geraldine M
GM
O'Connor
Department of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia.
Lucy C
LC
Sullivan
Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Clayton, VIC, Australia.|ARC Centre of Excellence in Advanced Molecular Imaging, Monash University, Clayton, VIC, Australia.
Phillip
P
Pymm
Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Clayton, VIC, Australia.|ARC Centre of Excellence in Advanced Molecular Imaging, Monash University, Clayton, VIC, Australia.|Institute of Infection and Immunity, Cardiff University School of Medicine, Cardiff, UK.
Jamie
J
Rossjohn
Department of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia.
Andrew G
AG
Brooks
D000818:Animals; D006680:HLA Antigens / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D008024:Ligands; D008958:Models, Molecular; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D055607:Receptors, Natural Killer Cell / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism
D006680:HLA Antigens; D015395:Histocompatibility Antigens Class I; D008024:Ligands; D055607:Receptors, Natural Killer Cell
CD94-NKG2; human leukocyte antigen; killer cell immunoglobulin-like receptors; natural killer cell receptors