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

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 t...

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Autores principales: 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., Purcell, Anthony W.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6224591/
https://www.ncbi.nlm.nih.gov/pubmed/30410026
http://dx.doi.org/10.1038/s41467-018-07109-w
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author 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.
Purcell, Anthony W.
author_facet 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.
Purcell, Anthony W.
author_sort Illing, Patricia T.
collection PubMed
description 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.
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spelling pubmed-62245912018-11-13 HLA-B57 micropolymorphism defines the sequence and conformational breadth of the immunopeptidome 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. Purcell, Anthony W. Nat Commun Article 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. Nature Publishing Group UK 2018-11-08 /pmc/articles/PMC6224591/ /pubmed/30410026 http://dx.doi.org/10.1038/s41467-018-07109-w Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle 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.
Purcell, Anthony W.
HLA-B57 micropolymorphism defines the sequence and conformational breadth of the immunopeptidome
title HLA-B57 micropolymorphism defines the sequence and conformational breadth of the immunopeptidome
title_full HLA-B57 micropolymorphism defines the sequence and conformational breadth of the immunopeptidome
title_fullStr HLA-B57 micropolymorphism defines the sequence and conformational breadth of the immunopeptidome
title_full_unstemmed HLA-B57 micropolymorphism defines the sequence and conformational breadth of the immunopeptidome
title_short HLA-B57 micropolymorphism defines the sequence and conformational breadth of the immunopeptidome
title_sort hla-b57 micropolymorphism defines the sequence and conformational breadth of the immunopeptidome
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6224591/
https://www.ncbi.nlm.nih.gov/pubmed/30410026
http://dx.doi.org/10.1038/s41467-018-07109-w
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