title: KIR3DL1 polymorphisms that affect NK cell inhibition by HLA-Bw4 ligand.
abstract: The killer cell Ig-like receptor (KIR) gene family encodes MHC class I receptors expressed by NK cells and several T cell subpopulations. Factors contributing to human KIR haplotype diversity are differences in gene number, gene content, and allelic polymorphism. Whereas functional and clinical consequences of the first two factors are established, knowledge of the effects of KIR gene polymorphism is limited to special cases in which signaling function is reversed or cell surface expression lost. In this study we use retrovirally transduced human cell lines to show that 3DL1*002 is a stronger inhibitory receptor for HLA-Bw4 ligands than 3DL1*007. Analysis of mutant 3DL1*002 and 3DL1*007 molecules demonstrates that residue 238 in the D2 domain and 320 in the transmembrane region contribute to the difference in receptor strength. Neither position 238 nor 320 is predicted to interact directly with HLA-Bw4 ligand. This study also revealed that KIR3DL1 and LILRB1 both contribute to developing an inhibitory response to HLA-Bw4 ligands.
authors.affiliation: Department of Structural Biology, Stanford University, Stanford, CA 94305-5126, USA. wcarr@itsa.ucsf.edu
authors.forename: William Henry
authors.initials: WH
authors.lastname: Carr
authors.forename: Marcelo Jorge
authors.initials: MJ
authors.lastname: Pando
authors.forename: Peter
authors.initials: P
authors.lastname: Parham
mesh_terms: D000483:Alleles; D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D015235:HLA-B Antigens / Q000378:metabolism*; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology / Q000502:physiology*; D000075362:Leukocyte Immunoglobulin-like Receptor B1; D008024:Ligands; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic; D017434:Protein Structure, Tertiary; D011971:Receptors, Immunologic / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D054340:Receptors, KIR; D054341:Receptors, KIR3DL1
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D015235:HLA-B Antigens; C042388:HLA-Bw4 antigen; D015395:Histocompatibility Antigens Class I; C515083:KIR3DL1 protein, human; C105299:LILRB1 protein, human; D000075362:Leukocyte Immunoglobulin-like Receptor B1; D008024:Ligands; D011971:Receptors, Immunologic; D054340:Receptors, KIR; D054341:Receptors, KIR3DL1