Killer Immunoglobulin Receptor 3DL1-mediated recognition of Human Leukocyte Antigen B

Members of the Killer Immunoglobulin-Like Receptor (KIR) family, a large group of polymorphic receptors expressed on Natural Killer (NK) cells, recognise particular peptide-laden Human Leukocyte Antigen (pHLA) class I molecules and play a pivotal role in innate immune responses1. Allelic variation and extensive polymorphism within the three-domain KIR family (KIR3D, domains D0–D1–D2) affects pHLA binding specificity and is linked to the control of viral replication and the treatment outcome of certain haematological malignancies1–3. We describe the structure of the KIR3DL1 receptor, bound to HLA-B*5701 complexed with a selfpeptide. KIR3DL1 clamped around the C-terminal end of the HLA-B*5701 antigen (Ag)-binding cleft, resulting in two discontinuous footprints on the pHLA. Firstly, the D0 domain, a distinguishing feature of the KIR3D family, extended towards 2-microglobulin and abutted a Joint senior and corresponding authors: [email protected], [email protected]. Supplementary Information is linked to the online version of this paper at www.nature.com/nature. Author Contributions J.V. solved the structure, undertook analysis, performed experiments and contributed to manuscript preparation. H.H.R., T.B., R.C.D., R.B., P.M.S., M.A.O., J.M.L.W., C.M.H., J.L., S.M.M, S.G., and C.S.C performed experiments and/or analyzed data. G.O’C., D.A.P., B.A.P.L. and D.W.M. performed experiments and/or analysed data and contributed to the writing of the manuscript; A.G.B. and J.R. contributed to the design and interpretation of data, project management, and writing of the manuscript.