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

Journal article


Illing, Patricia T., Pymm, Phillip, Croft, Nathan P., Hilton, Hugo G., Jojic, Vladimir, Han, Alex S., Mendoza, Juan L., Mifsud, Nicole A., Dudek, Nadine L., McCluskey, James, Parham, Peter, Rossjohn, Jamie, Vivian, Julian P. and Purcell, Anthony W.. (2018). HLA-B57 micropolymorphism defines the sequence and conformational breadth of the immunopeptidome. Nature Communications. 9(1), p. Article 4693. https://doi.org/10.1038/s41467-018-07109-w
AuthorsIlling, Patricia T., Pymm, Phillip, Croft, Nathan P., Hilton, Hugo G., Jojic, Vladimir, Han, Alex S., Mendoza, Juan L., Mifsud, Nicole A., Dudek, Nadine L., McCluskey, James, Parham, Peter, Rossjohn, Jamie, Vivian, Julian P. and Purcell, Anthony W.
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 approach. The peptide repertoires show marked qualitative overlap, with 982 peptides presented by all allomorphs. However, differences in peptide abundance, HLA-peptide stability, and HLA-bound conformation demonstrate that HLA micropolymorphism impacts more than simply the range of peptide ligands. These differences provide grounds for distinct immune reactivity and insights into the capacity of micropolymorphism to diversify immune outcomes.

Year2018
JournalNature Communications
Journal citation9 (1), p. Article 4693
PublisherSpringer Nature
ISSN2041-1723
Digital Object Identifier (DOI)https://doi.org/10.1038/s41467-018-07109-w
PubMed ID30410026
Scopus EID2-s2.0-85056270495
PubMed Central IDPMC6224591
Open accessPublished as ‘gold’ (paid) open access
Page range1-13
Publisher's version
License
File Access Level
Open
Output statusPublished
Publication dates
Online08 Nov 2018
Publication process dates
Accepted12 Oct 2018
Deposited28 Nov 2023
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