Natural killer cell recognition of HLA class I molecules.
Human NK cells express multiple receptors that interact with HLA class I molecules. These receptors belong to one of two major protein superfamilies, the immunoglobulin superfamily or the C type lectin superfamily. The killer cell immunoglobulin-like receptor (KIR) family predominantly recognise classical HLA class I molecules and different family members interact with discrete HLA class I allotypes. The solution of the crystal structure of KIR2DL2 in complex with its ligand, HLA-Cw3 has provided the molecular details of a KIR/class I interaction. The interaction site spans both the alpha1 and alpha2 helices of class I and the KIR makes direct contact with peptide residues 7 and 8. The allotype specificity of KIR2DL2 for HLA-Cw3 is the result of a single hydrogen bond from Lys44 of the KIR to Asn80 of HLA-C as all other HLA-C residues that contact KIR are conserved. The lectin-like CD94/NKG2 receptors specifically interact with the non-classical class I molecule, HLA-E. Cell surface expression of HLA-E is dependent on the expression of other class I molecules as they are the major source of HLA-E binding peptides in normal cells. Consequently recognition of HLA-E by the CD94/NKG2 receptors allows NK cells to indirectly monitor the expression of a broad array of class I molecules. While the molecular interactions underlying ligand recognition by both KIR and CD94/NKG2 receptors are likely to be distinct, recognition of class I by both families of receptors appears peptide dependent. This suggest that cells that lack class I and also those that are impaired in their ability to load class I molecules with peptide will become targets for NK-mediated destruction.
Department of Microbiology and Immunology, University of Melbourne, Victoria, Australia. agbrooks@unimelb.edu.au
A G
AG
Brooks
J C
JC
Boyington
P D
PD
Sun
D000595:Amino Acid Sequence; D015703:Antigens, CD / Q000276:immunology; D001665:Binding Sites; D003602:Cytotoxicity, Immunologic; D019281:Dimerization; D006680:HLA Antigens / Q000737:chemistry / Q000276:immunology; D015236:HLA-C Antigens / Q000737:chemistry / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000737:chemistry / Q000276:immunology*; D006801:Humans; D006860:Hydrogen Bonding; D037181:Lectins, C-Type; D000075362:Leukocyte Immunoglobulin-like Receptor B1; D046911:Macromolecular Substances; D008562:Membrane Glycoproteins / Q000276:immunology; D008958:Models, Molecular; D008969:Molecular Sequence Data; D005810:Multigene Family; D055654:NK Cell Lectin-Like Receptor Subfamily C; D051920:NK Cell Lectin-Like Receptor Subfamily D; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D011971:Receptors, Immunologic / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D054340:Receptors, KIR; D054343:Receptors, KIR2DL2; D055607:Receptors, Natural Killer Cell; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013329:Structure-Activity Relationship; D015032:Zinc / Q000502:physiology; D000097625:HLA-E Antigens
D015703:Antigens, CD; D006680:HLA Antigens; D015236:HLA-C Antigens; D015395:Histocompatibility Antigens Class I; D037181:Lectins, C-Type; D000075362:Leukocyte Immunoglobulin-like Receptor B1; D046911:Macromolecular Substances; D008562:Membrane Glycoproteins; D055654:NK Cell Lectin-Like Receptor Subfamily C; D051920:NK Cell Lectin-Like Receptor Subfamily D; D010446:Peptide Fragments; D011971:Receptors, Immunologic; D054340:Receptors, KIR; D054343:Receptors, KIR2DL2; D055607:Receptors, Natural Killer Cell; D015032:Zinc; D000097625:HLA-E Antigens; C038653:HLA-C*03 antigen; C515077:KIR2DL2 protein, human; C527054:KLRC1 protein, human; C497869:KLRD1 protein, human; C105299:LILRB1 protein, human