The D0 domain of KIR3D acts as a major histocompatibility complex class I binding enhancer.
In contrast to the KIR2D:HLA-C interaction, little is known of KIR3DL1's interaction with HLA-B or the role of D0, the domain not present in KIR2D. Differences in the strength and specificity for major histocompatibility complex class I of KIR3DL1 and its common chimpanzee homologue Pt-KIR3DL1/2 were exploited to address these questions. Domain-swap, deletion, and site-directed mutants of KIR3DL1 were analyzed for HLA-B binding using a novel, positively signaling cell-cell binding assay. Natural 'deletion' of residues 50 and 51 from its D0 domain causes Pt-KIR3DL1/2 to bind Bw4(+) HLA-B allotypes more avidly than does KIR3DL1. Deletion of these residues from KIR3DL1, or their substitution for alanine, enhanced binding of Bw4(+) HLA-B. None of 15 different point mutations in D0 abrogated KIR3DL1 binding to Bw4(+) HLA-B. In contrast point mutations in the D1 and D2 domains of KIR3DL1, made from knowledge of KIR2D:HLA-C interactions, disrupted binding to Bw4(+) HLA-B. The results are consistent with a model in which D1 and D2 make the principal contacts between KIR3DL1 and HLA-B while D0 acts through a different mechanism to enhance the interaction. This modulatory role for D0 is compatible with natural loss of expression of the D0 domain, a repeated event in the evolution of functional KIR genes.
Khakoo
Salim I
SI
Department of Structural Biology, Stanford University School of Medicine, CA 94305, USA.
Geller
Ron
R
Shin
Sunny
S
Jenkins
Jomaquai A
JA
Parham
Peter
P
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D017931:DNA Primers; D015235:HLA-B Antigens / Q000276:immunology*; D006801:Humans; D019169:Jurkat Cells; D002679:Pan troglodytes; D016133:Polymerase Chain Reaction; D011971:Receptors, Immunologic / Q000737:chemistry / Q000276:immunology*; D054340:Receptors, KIR; D054341:Receptors, KIR3DL1; D011993:Recombinant Fusion Proteins / Q000276:immunology; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014162:Transfection
D017931:DNA Primers; D015235:HLA-B Antigens; C515083:KIR3DL1 protein, human; D011971:Receptors, Immunologic; D054340:Receptors, KIR; D054341:Receptors, KIR3DL1; D011993:Recombinant Fusion Proteins