Abstract
Natural killer (NK)-cell function is regulated by NK receptors that recognize MHC class I (MHC-I) molecules on target cells. Two structurally distinct families of NK receptors have been identified, the immunoglobulin-like family (killer cell immunoglobulin-like receptors (KIRs), leukocyte immunoglobulin-like receptors (LIRs)) and the C-type lectin-like family (Ly49, CD94/NKG2A, NKG2D, CD69). Recently, the three-dimensional structures of several NK receptors were determined, in free form or bound to MHC-I. These include those of unbound KIRs, NKG2D, CD69, LIR-1 and the CD94 subunit of the CD94/NKG2A heterodimer. Together, these structures define the basic molecular architecture of both the immunoglobulin-like and C-type lectin-like families of NK receptors. In addition, crystal structures have been reported for the complex between Ly49A and H-2Dd, and for KIR2DL2 bound to HLA-Cw3. The complex structures provide a framework for understanding MHC-I recognition by NK receptors from both families and reveal striking differences in the nature of this recognition, despite the receptors' functional similarity.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
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Review
MeSH terms
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Amino Acid Sequence
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Animals
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Antigens, CD / chemistry
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Antigens, CD / genetics
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Antigens, CD / metabolism
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Antigens, Ly*
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Binding Sites
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Carrier Proteins / chemistry
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Carrier Proteins / genetics
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Carrier Proteins / metabolism
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H-2 Antigens / chemistry
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H-2 Antigens / metabolism
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HLA-C Antigens / chemistry
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HLA-C Antigens / metabolism
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Histocompatibility Antigen H-2D
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Histocompatibility Antigens Class I* / chemistry
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Histocompatibility Antigens Class I* / metabolism
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Humans
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Killer Cells, Natural / immunology*
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Lectins, C-Type
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Leukocyte Immunoglobulin-like Receptor B1
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Ligands
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Macromolecular Substances
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Membrane Proteins / chemistry
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Membrane Proteins / genetics
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Membrane Proteins / metabolism
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Mice
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Models, Molecular
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Molecular Sequence Data
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Molecular Structure
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NK Cell Lectin-Like Receptor Subfamily A
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Receptors, Immunologic / chemistry*
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Receptors, Immunologic / genetics
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Receptors, Immunologic / metabolism
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Receptors, KIR
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Receptors, KIR2DL2
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Receptors, NK Cell Lectin-Like
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Sequence Homology, Amino Acid
Substances
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Antigens, CD
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Antigens, Ly
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Carrier Proteins
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H-2 Antigens
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HLA-C Antigens
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HLA-C*03 antigen
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Histocompatibility Antigen H-2D
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Histocompatibility Antigens Class I
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KIR2DL2 protein, human
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Klra1 protein, mouse
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LILRB1 protein, human
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Lectins, C-Type
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Leukocyte Immunoglobulin-like Receptor B1
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Ligands
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Macromolecular Substances
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Membrane Proteins
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NK Cell Lectin-Like Receptor Subfamily A
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Receptors, Immunologic
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Receptors, KIR
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Receptors, KIR2DL2
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Receptors, NK Cell Lectin-Like