Journal article

HLA-B57 micropolymorphism defines the sequence and conformational breadth of the immunopeptidome

Patricia T Illing, Phillip Pymm, Nathan P Croft, Hugo G Hilton, Vladimir Jojic, Alex S Han, Juan L Mendoza, Nicole A Mifsud, Nadine L Dudek, James McCluskey, Peter Parham, Jamie Rossjohn, Julian P Vivian, Anthony W Purcell

NATURE COMMUNICATIONS | NATURE PUBLISHING GROUP | Published : 2018

Abstract

Immunophenotypic differences between closely related human leukocyte antigen (HLA) alleles have been associated with divergent clinical outcomes in infection, autoimmunity, transplantation and drug hypersensitivity. Here we explore the impact of micropolymorphism on peptide antigen presentation by three closely related HLA molecules, HLA-B*57:01, HLA-B*57:03 and HLA-B*58:01, that are differentially associated with the HIV elite controller phenotype and adverse drug reactions. For each allotype, we mine HLA ligand data sets derived from the same parental cell proteome to define qualitative differences in peptide presentation using classical peptide binding motifs and an unbiased statistical a..

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Awarded by NHMRC


Awarded by NIH


Awarded by NATIONAL CANCER INSTITUTE


Awarded by NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES


Funding Acknowledgements

Thank you to Tracy Josephs for assistance with protocols for the thermal stability experiments. This work was funded by a NHMRC Project grant (1063829) to A.W.P. and J.P.V., and by NIH grant AI22039 to P.P. A.W.P. is supported by a NHMRC Senior Research Fellowship (1044215). P.T.I. was supported by a NHMRC Early Career Fellowship (1072159). J.R. is supported by an Australian Research Council Australian Laureate Fellowship. J.L.M. is supported by NIH award K01CA175127. J.M. was supported by a NHMRC Project Grant (1120467) and Program Grant (1113293).