PMID: 22020283

 

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Title : Killer cell immunoglobulin-like receptor 3DL1-mediated recognition of human leukocyte antigen B . Members of the killer cell immunoglobulin-like receptor ( KIR ) family, a large group of polymorphic receptors expressed on natural killer (NK) cells, recognize particular peptide-laden human leukocyte antigen (p HLA ) class I molecules and have a pivotal role in innate immune responses

Abstract :
  1. Allelic variation and extensive polymorphism within the three-domain KIR family (KIR3D, domains D0-D1-D2) affects p HLA binding specificity and is linked to the control of viral replication and the treatment outcome of certain haematological malignancies
  2. Here we describe the structure of a human KIR3DL1 receptor bound to HLA-B *5701 complexed with a self-peptide
  3. KIR3DL1 clamped around the carboxy-terminal end of the HLA-B *5701 antigen-binding cleft, resulting in two discontinuous footprints on the p HLA
  4. First, the D0 domain , a distinguishing feature of the KIR3D family, extended towards β2-microglobulin and abutted a region of the HLA molecule with limited polymorphism, thereby acting as an 'innate HLA sensor' domain
  5. Second, whereas the D2- HLA-B *5701 interface exhibited a high degree of complementarity, the D1-p HLA-B *5701 contacts were suboptimal and accommodated a degree of sequence variation both within the peptide and the polymorphic region of the HLA molecule
  6. Although the two-domain KIR ( KIR2D ) and KIR3DL1 docked similarly onto HLA-C and HLA-B respectively, the corresponding D1-mediated interactions differed markedly, thereby providing insight into the specificity of KIR3DL1 for discrete HLA-A and HLA-B allotypes
  7. Collectively, in association with extensive mutagenesis studies at the KIR3DL1-p HLA-B *5701 interface, we provide a framework for understanding the intricate interplay between peptide variability, KIR3D and HLA polymorphism in determining the specificity requirements of this essential innate interaction that is conserved across primate species