• Killer cell Immunoglobulin-like Receptor 3DL1 polymorphism defines distinct hierarchies of HLA class I recognition

      Saunders, Philippa M.; Pymm, Phillip; Pietra, Gabriella; Hughes, Victoria A.; Hitchen, Corinne; O'Connor, Geraldine M.; Loiacono, Fabrizio; Widjaja, Jacqueline M.; Price, David A.; Falco, Michela; et al. (Rockefeller University Press, 2016-04-04)
      NK cells play a key role in immunity, but how HLA-I and KIR3DL1 polymorphism impacts on disease outcome remains unclear. KIR3DL1 (*001/*005/*015) tetramers were screened for reactivity against a panel of HLA-I molecules. This revealed different and distinct hierarchies of specificity for each KIR3DL1 allotype, with KIR3DL1*005 recognising the widest array of HLA-I ligands. These differences were further reflected in unctional studies utilising NK clones expressing these specific KIR3DL1 allotypes. Unexpectedly, the Ile/Thr80 dimorphism in the Bw4-motif did not categorically define strong/weak KIR3DL1 recognition. Although the KIR3DL1*001, *005 and *015 polymorphisms are remote from the KIR3DL1-HLA-I interface, the structures of these three KIR3DL1-HLA-I complexes showed that the broader HLA-I specificity of KIR3DL1*005 correlated with an altered KIR3DL1*005 interdomain positioning and increased mobility within its ligand-binding site. Collectively, we provide a generic framework for understanding the impact of KIR3DL1 polymorphism on the recognition of HLA-I allomorphs.