Natural killer cell recognition of HLA class I molecules.

A G Brooks, J C Boyington, P D Sun

Journal: Reviews in immunogenetics 2001;2(3):433-48

PMID: 11256749

Abstract

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.

Address: Department of Microbiology and Immunology, University of Melbourne, Victoria, Australia. [email protected]

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Research Materials:

https://antibodies.cancer.gov/detail/CPTC-HLA-DQA1...

MeSH Terms: Amino Acid Sequence, Antigens, CD, Binding Sites, Cytotoxicity, Immunologic, Dimerization, HLA Antigens, HLA-C Antigens, Histocompatibility Antigens Class I, Humans, Hydrogen Bonding, Lectins, C-Type, Leukocyte Immunoglobulin-like Receptor B1, Macromolecular Substances, Membrane Glycoproteins, Models, Molecular, Molecular Sequence Data, Multigene Family, NK Cell Lectin-Like Receptor Subfamily C, NK Cell Lectin-Like Receptor Subfamily D, Peptide Fragments, Protein Binding, Protein Conformation, Protein Structure, Tertiary, Receptors, Immunologic, Receptors, KIR, Receptors, KIR2DL2, Receptors, Natural Killer Cell, Sequence Alignment, Sequence Homology, Amino Acid, Structure-Activity Relationship, Zinc, HLA-E Antigens