Killer cell immunoglobulin-like receptor 3DL1 polymorphism defines distinct hierarchies of HLA class I recognition

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Saunders, PM; Pymm, P; Pietra, G; Hughes, VA; Hitchen, C; O'Connor, GM; Loiacono, F; Widjaja, J; Price, DA; Falco, M; ...Date
2016-05-02Source Title
Journal of Experimental MedicinePublisher
ROCKEFELLER UNIV PRESSUniversity of Melbourne Author/s
Saunders, Philippa; Widjaja, Jacqueline; Brooks, Andrew; O'CONNOR, GERALDINE; Rossjohn, JamieAffiliation
Microbiology and ImmunologyMetadata
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Saunders, P. M., Pymm, P., Pietra, G., Hughes, V. A., Hitchen, C., O'Connor, G. M., Loiacono, F., Widjaja, J., Price, D. A., Falco, M., Mingari, M. C., Moretta, L., McVicar, D. W., Rossjohn, J., Brooks, A. G. & Vivian, J. P. (2016). Killer cell immunoglobulin-like receptor 3DL1 polymorphism defines distinct hierarchies of HLA class I recognition. JOURNAL OF EXPERIMENTAL MEDICINE, 213 (5), pp.791-807. https://doi.org/10.1084/jem.20152023.Access Status
Open AccessAbstract
Natural killer (NK) cells play a key role in immunity, but how HLA class I (HLA-I) and killer cell immunoglobulin-like receptor 3DL1 (KIR3DL1) polymorphism impacts 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 recognizing the widest array of HLA-I ligands. These differences were further reflected in functional studies using 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.
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