Journal article

The molecular basis of how buried human leukocyte antigen polymorphism modulates natural killer cell function

Philippa M Saunders, Bruce J MacLachlan, Phillip Pymm, Patricia T Illing, Yuanchen Deng, Shu Cheng Wong, Clare VL Oates, Anthony W Purcell, Jamie Rossjohn, Julian P Vivian, Andrew G Brooks

Proceedings of the National Academy of Sciences of the United States of America | NATL ACAD SCIENCES | Published : 2020


Micropolymorphisms within human leukocyte antigen (HLA) class I molecules can change the architecture of the peptide-binding cleft, leading to differences in peptide presentation and T cell recognition. The impact of such HLA variation on natural killer (NK) cell recognition remains unclear. Given the differential association of HLA-B*57:01 and HLA-B*57:03 with the control of HIV, recognition of these HLA-B57 allomorphs by the killer cell immunoglobulin-like receptor (KIR) 3DL1 was compared. Despite differing by only two polymorphic residues, both buried within the peptide-binding cleft, HLA-B*57:01 more potently inhibited NK cell activation. Direct-binding studies showed KIR3DL1 to preferen..

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Funding Acknowledgements

This work was funded by grants from the National Health and Medical Research Council (to J.R., A.G.B., and J.P.V.), the Australian Research Council (to A.G.B.), and the worldwide cancer research organization. J.R. is supported by an Australian Research Council Laureate Fellowship, and A.W.P. by a National Health and Medical Research Council Principal Research Fellowship. This research was undertaken in part using the MX2 beamline at the Australian Synchrotron, part of the Australian Nuclear Science and Technology Organisation, and made use of the Australian Cancer Research Foundation detector. We thank the staff at the Monash Macromolecular Crystallization Facility.