Citrullination only infrequently impacts peptide binding to HLA class II MHC

Autores
Sidney, John; Becart, Stephane; Zhou, Mimi; Duffy, Karen; Lindvall, Mikaela; Moore, Erin C.; Moore, Eugene L.; Rao, Tadimeti; Rao, Navin; Nielsen, Morten; Peters, Bjoern; Sette, Alessandro
Año de publicación
2017
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
It has been hypothesized that HLA class II alleles associated with rheumatoid arthritis (RA) preferentially present self-antigens altered by post-translational modification, such as citrullination. To understand the role of citrullination we tested four RA-associated citrullinated epitopes and their corresponding wild-type version for binding to 28 common HLA class II. Binding patterns were variable, and no consistent impact of citrullination was identified. Indeed, in one case citrullination significantly increased binding compared to the WT peptide, in another citrullination was associated with a reduction in promiscuity by 40%. For a more comprehensive analysis, we tested over 200 citrullinated peptides derived from vimentin and collagen II for their capacity to bind the RA-associated shared epitope alleles DRB1∗01:01 and DRB1∗04:01. The overall effect of citrullination on binding was found to be relatively minor, and only rarely associated with 3-fold increases or decreases in affinity. Previous studies have suggested that citrullination of MHC anchor residues, in particular P4, is associated with generation of novel RA-associated epitopes. However, analysis of the predicted MHC-binding cores of all peptides tested found that in modified peptides with increased binding affinity the citrullinated residue was predicted to occupy an anchor position in only a minority of cases. Finally, we also show that identification of citrullinated peptide binders could be facilitated by using the NetMHCIIpan 3.1 algorithm, representing citrullination as a wildcard. Our studies identify a total of 117 citrullinated peptides that bound RA-associated alleles with an affinity of 1000 nM or better.
Fil: Sidney, John. La Jolla Institute for Allergy and Immunology; Estados Unidos
Fil: Becart, Stephane. Janssen Research & Development; Estados Unidos
Fil: Zhou, Mimi. Janssen Research & Development; Estados Unidos
Fil: Duffy, Karen. Janssen Research & Development; Estados Unidos
Fil: Lindvall, Mikaela. La Jolla Institute for Allergy and Immunology; Estados Unidos
Fil: Moore, Erin C.. La Jolla Institute for Allergy and Immunology; Estados Unidos
Fil: Moore, Eugene L.. La Jolla Institute for Allergy and Immunology; Estados Unidos
Fil: Rao, Tadimeti. Janssen Research & Development; Estados Unidos
Fil: Rao, Navin. Janssen Research & Development; Estados Unidos
Fil: Nielsen, Morten. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; Argentina. Technical University of Denmark; Dinamarca
Fil: Peters, Bjoern. La Jolla Institute for Allergy and Immunology; Estados Unidos
Fil: Sette, Alessandro. La Jolla Institute for Allergy and Immunology; Estados Unidos
Materia
MHC class II
Citrullination
Prediction
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/48676
Acceder
id CONICETDig_877ce3376ca77f82f2bc24823511386e
oai_identifier_str oai:ri.conicet.gov.ar:11336/48676
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Citrullination only infrequently impacts peptide binding to HLA class II MHCSidney, JohnBecart, StephaneZhou, MimiDuffy, KarenLindvall, MikaelaMoore, Erin C.Moore, Eugene L.Rao, TadimetiRao, NavinNielsen, MortenPeters, BjoernSette, AlessandroMHC class IICitrullinationPredictionhttps://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3It has been hypothesized that HLA class II alleles associated with rheumatoid arthritis (RA) preferentially present self-antigens altered by post-translational modification, such as citrullination. To understand the role of citrullination we tested four RA-associated citrullinated epitopes and their corresponding wild-type version for binding to 28 common HLA class II. Binding patterns were variable, and no consistent impact of citrullination was identified. Indeed, in one case citrullination significantly increased binding compared to the WT peptide, in another citrullination was associated with a reduction in promiscuity by 40%. For a more comprehensive analysis, we tested over 200 citrullinated peptides derived from vimentin and collagen II for their capacity to bind the RA-associated shared epitope alleles DRB1∗01:01 and DRB1∗04:01. The overall effect of citrullination on binding was found to be relatively minor, and only rarely associated with 3-fold increases or decreases in affinity. Previous studies have suggested that citrullination of MHC anchor residues, in particular P4, is associated with generation of novel RA-associated epitopes. However, analysis of the predicted MHC-binding cores of all peptides tested found that in modified peptides with increased binding affinity the citrullinated residue was predicted to occupy an anchor position in only a minority of cases. Finally, we also show that identification of citrullinated peptide binders could be facilitated by using the NetMHCIIpan 3.1 algorithm, representing citrullination as a wildcard. Our studies identify a total of 117 citrullinated peptides that bound RA-associated alleles with an affinity of 1000 nM or better.Fil: Sidney, John. La Jolla Institute for Allergy and Immunology; Estados UnidosFil: Becart, Stephane. Janssen Research & Development; Estados UnidosFil: Zhou, Mimi. Janssen Research & Development; Estados UnidosFil: Duffy, Karen. Janssen Research & Development; Estados UnidosFil: Lindvall, Mikaela. La Jolla Institute for Allergy and Immunology; Estados UnidosFil: Moore, Erin C.. La Jolla Institute for Allergy and Immunology; Estados UnidosFil: Moore, Eugene L.. La Jolla Institute for Allergy and Immunology; Estados UnidosFil: Rao, Tadimeti. Janssen Research & Development; Estados UnidosFil: Rao, Navin. Janssen Research & Development; Estados UnidosFil: Nielsen, Morten. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; Argentina. Technical University of Denmark; DinamarcaFil: Peters, Bjoern. La Jolla Institute for Allergy and Immunology; Estados UnidosFil: Sette, Alessandro. La Jolla Institute for Allergy and Immunology; Estados UnidosPublic Library of Science2017-05info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/48676Sidney, John; Becart, Stephane; Zhou, Mimi; Duffy, Karen; Lindvall, Mikaela; et al.; Citrullination only infrequently impacts peptide binding to HLA class II MHC; Public Library of Science; Plos One; 12; 5; 5-20171932-6203CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1371/journal.pone.0177140info:eu-repo/semantics/altIdentifier/url/http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0177140info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:44:35Zoai:ri.conicet.gov.ar:11336/48676instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 09:44:36.277CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Citrullination only infrequently impacts peptide binding to HLA class II MHC
title Citrullination only infrequently impacts peptide binding to HLA class II MHC
spellingShingle Citrullination only infrequently impacts peptide binding to HLA class II MHC
Sidney, John
MHC class II
Citrullination
Prediction
title_short Citrullination only infrequently impacts peptide binding to HLA class II MHC
title_full Citrullination only infrequently impacts peptide binding to HLA class II MHC
title_fullStr Citrullination only infrequently impacts peptide binding to HLA class II MHC
title_full_unstemmed Citrullination only infrequently impacts peptide binding to HLA class II MHC
title_sort Citrullination only infrequently impacts peptide binding to HLA class II MHC
dc.creator.none.fl_str_mv Sidney, John
Becart, Stephane
Zhou, Mimi
Duffy, Karen
Lindvall, Mikaela
Moore, Erin C.
Moore, Eugene L.
Rao, Tadimeti
Rao, Navin
Nielsen, Morten
Peters, Bjoern
Sette, Alessandro
author Sidney, John
author_facet Sidney, John
Becart, Stephane
Zhou, Mimi
Duffy, Karen
Lindvall, Mikaela
Moore, Erin C.
Moore, Eugene L.
Rao, Tadimeti
Rao, Navin
Nielsen, Morten
Peters, Bjoern
Sette, Alessandro
author_role author
author2 Becart, Stephane
Zhou, Mimi
Duffy, Karen
Lindvall, Mikaela
Moore, Erin C.
Moore, Eugene L.
Rao, Tadimeti
Rao, Navin
Nielsen, Morten
Peters, Bjoern
Sette, Alessandro
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv MHC class II
Citrullination
Prediction
topic MHC class II
Citrullination
Prediction
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv It has been hypothesized that HLA class II alleles associated with rheumatoid arthritis (RA) preferentially present self-antigens altered by post-translational modification, such as citrullination. To understand the role of citrullination we tested four RA-associated citrullinated epitopes and their corresponding wild-type version for binding to 28 common HLA class II. Binding patterns were variable, and no consistent impact of citrullination was identified. Indeed, in one case citrullination significantly increased binding compared to the WT peptide, in another citrullination was associated with a reduction in promiscuity by 40%. For a more comprehensive analysis, we tested over 200 citrullinated peptides derived from vimentin and collagen II for their capacity to bind the RA-associated shared epitope alleles DRB1∗01:01 and DRB1∗04:01. The overall effect of citrullination on binding was found to be relatively minor, and only rarely associated with 3-fold increases or decreases in affinity. Previous studies have suggested that citrullination of MHC anchor residues, in particular P4, is associated with generation of novel RA-associated epitopes. However, analysis of the predicted MHC-binding cores of all peptides tested found that in modified peptides with increased binding affinity the citrullinated residue was predicted to occupy an anchor position in only a minority of cases. Finally, we also show that identification of citrullinated peptide binders could be facilitated by using the NetMHCIIpan 3.1 algorithm, representing citrullination as a wildcard. Our studies identify a total of 117 citrullinated peptides that bound RA-associated alleles with an affinity of 1000 nM or better.
Fil: Sidney, John. La Jolla Institute for Allergy and Immunology; Estados Unidos
Fil: Becart, Stephane. Janssen Research & Development; Estados Unidos
Fil: Zhou, Mimi. Janssen Research & Development; Estados Unidos
Fil: Duffy, Karen. Janssen Research & Development; Estados Unidos
Fil: Lindvall, Mikaela. La Jolla Institute for Allergy and Immunology; Estados Unidos
Fil: Moore, Erin C.. La Jolla Institute for Allergy and Immunology; Estados Unidos
Fil: Moore, Eugene L.. La Jolla Institute for Allergy and Immunology; Estados Unidos
Fil: Rao, Tadimeti. Janssen Research & Development; Estados Unidos
Fil: Rao, Navin. Janssen Research & Development; Estados Unidos
Fil: Nielsen, Morten. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; Argentina. Technical University of Denmark; Dinamarca
Fil: Peters, Bjoern. La Jolla Institute for Allergy and Immunology; Estados Unidos
Fil: Sette, Alessandro. La Jolla Institute for Allergy and Immunology; Estados Unidos
description It has been hypothesized that HLA class II alleles associated with rheumatoid arthritis (RA) preferentially present self-antigens altered by post-translational modification, such as citrullination. To understand the role of citrullination we tested four RA-associated citrullinated epitopes and their corresponding wild-type version for binding to 28 common HLA class II. Binding patterns were variable, and no consistent impact of citrullination was identified. Indeed, in one case citrullination significantly increased binding compared to the WT peptide, in another citrullination was associated with a reduction in promiscuity by 40%. For a more comprehensive analysis, we tested over 200 citrullinated peptides derived from vimentin and collagen II for their capacity to bind the RA-associated shared epitope alleles DRB1∗01:01 and DRB1∗04:01. The overall effect of citrullination on binding was found to be relatively minor, and only rarely associated with 3-fold increases or decreases in affinity. Previous studies have suggested that citrullination of MHC anchor residues, in particular P4, is associated with generation of novel RA-associated epitopes. However, analysis of the predicted MHC-binding cores of all peptides tested found that in modified peptides with increased binding affinity the citrullinated residue was predicted to occupy an anchor position in only a minority of cases. Finally, we also show that identification of citrullinated peptide binders could be facilitated by using the NetMHCIIpan 3.1 algorithm, representing citrullination as a wildcard. Our studies identify a total of 117 citrullinated peptides that bound RA-associated alleles with an affinity of 1000 nM or better.
publishDate 2017
dc.date.none.fl_str_mv 2017-05
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/48676
Sidney, John; Becart, Stephane; Zhou, Mimi; Duffy, Karen; Lindvall, Mikaela; et al.; Citrullination only infrequently impacts peptide binding to HLA class II MHC; Public Library of Science; Plos One; 12; 5; 5-2017
1932-6203
CONICET Digital
CONICET
url http://hdl.handle.net/11336/48676
identifier_str_mv Sidney, John; Becart, Stephane; Zhou, Mimi; Duffy, Karen; Lindvall, Mikaela; et al.; Citrullination only infrequently impacts peptide binding to HLA class II MHC; Public Library of Science; Plos One; 12; 5; 5-2017
1932-6203
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1371/journal.pone.0177140
info:eu-repo/semantics/altIdentifier/url/http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0177140
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Public Library of Science
publisher.none.fl_str_mv Public Library of Science
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
_version_ 1842268677534121984
score 13.13397

Publicaciones similares