title: The first Ig domain of KIR3DL1 contacts MHC class I at a secondary site.
abstract: KIR3DL1 is a highly polymorphic inhibitory killer cell Ig-like receptor (KIR) implicated in resistance to viral diseases such as AIDS. KIR3DL1 contains three Ig domains and is specific for MHC class I (MHC-I) molecules belonging to the HLA-Bw4 serogroup. The receptor's second and third Ig domains confer the Bw4 specificity, but the role of the first Ig domain (D0) in ligand recognition has remained enigmatic. We found that KIR3DL1 expressed in YTS cells and as a soluble receptor can weakly recognize additional MHC-I molecules including HLA-B*0702 and HLA-G. This interaction is highly sensitive to blocking with Abs to the MHC-I α3-domain and the anti-KIR3DL1 Ab Z27, but not the canonical blocking Ab DX9. Using chimeric receptors between KIR3DL1 and KIR2DL1 expressed on YTS cells and as soluble Fc-fusion proteins, we show that the D0 domain confers the broad functional recognition and binding as well as the reactivity with Z27. These results suggest that the presence of a second and independent site of interaction between D0 and MHC-I and that MHC-I could bridge KIR3DL1 molecules together in a manner that facilitates signaling.
authors: Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, Alberta T6G 2S2, Canada.
authors: Li
authors: L
authors: Fu
authors: Bart
authors: B
authors: Hazes
authors: Deborah N
authors: DN
authors: Burshtyn
mesh_terms: D000818:Animals; D058846:Antibodies, Monoclonal, Murine-Derived / Q000276:immunology / Q000494:pharmacology; D057134:Antibodies, Neutralizing / Q000276:immunology / Q000494:pharmacology; D001665:Binding Sites; D019556:COS Cells; D002522:Chlorocebus aethiops; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D017434:Protein Structure, Tertiary; D054342:Receptors, KIR2DL1 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D054341:Receptors, KIR3DL1 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D057134:Antibodies, Neutralizing; D015395:Histocompatibility Antigens Class I; C093100:KIR2DL1 protein, human; C515083:KIR3DL1 protein, human; D054342:Receptors, KIR2DL1; D054341:Receptors, KIR3DL1; D011993:Recombinant Fusion Proteins