Killer cell immunoglobulin-like receptor 3DL1-mediated recognition of human leukocyte antigen B

摘要: Members of the killer cell immunoglobulin-like receptor (KIR) family, a large group polymorphic receptors expressed on natural (NK) cells, recognize particular peptide-laden human leukocyte antigen (pHLA) class I molecules and have pivotal role in innate immune responses1. Allelic variation extensive polymorphism within three-domain KIR family (KIR3D, domains D0–D1–D2) affects pHLA binding specificity is linked to control viral replication treatment outcome certain haematological malignancies1, 2, 3. Here we describe structure KIR3DL1 bound HLA-B*5701 complexed with self-peptide. clamped around carboxy-terminal end antigen-binding cleft, resulting two discontinuous footprints pHLA. First, D0 domain, distinguishing feature KIR3D extended towards β2-microglobulin abutted region HLA molecule limited polymorphism, thereby acting as an ‘innate sensor’ domain. Second, whereas D2–HLA-B*5701 interface exhibited high degree complementarity, D1–pHLA-B*5701 contacts were suboptimal accommodated sequence both peptide molecule. Although two-domain (KIR2D) docked similarly onto HLA-C4, 5 HLA-B respectively, corresponding D1-mediated interactions differed markedly, providing insight into for discrete HLA-A allotypes. Collectively, association mutagenesis studies at KIR3DL1–pHLA-B*5701 interface, provide framework understanding intricate interplay between variability, determining requirements this essential interaction that conserved across primate species.