Uncovering the peptide-binding specificities of HLA-C: a general strategy to determine the specificity of any MHC class I molecule

Autores
Rasmussen, Michael; Harndahl, Mikkel; Stryhn, Anette; Boucherma, Rachid; Nielsen, Lise Lotte; Lemonnier, François A.; Nielsen, Morten; Buus, Søren
Año de publicación
2014
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
MHC class I molecules (HLA-I in humans) present peptides derived from endogenous proteins to CTLs. Whereas the peptide-binding specificities of HLA-A and -B molecules have been studied extensively, little is known about HLA-C specificities. Combining a positional scanning combinatorial peptide library approach with a peptide–HLA-I dissociation assay, in this study we present a general strategy to determine the peptide-binding specificity of any MHC class I molecule. We applied this novel strategy to 17 of the most common HLA-C molecules, and for 16 of these we successfully generated matrices representing their peptide-binding motifs. The motifs prominently shared a conserved C-terminal primary anchor with hydrophobic amino acid residues, as well as one or more diverse primary and auxiliary anchors at P1, P2, P3, and/or P7. Matrices were used to generate a large panel of HLA-C–specific peptide-binding data and update our pan-specific NetMHCpan predictor, whose predictive performance was considerably improved with respect to peptide binding to HLA-C. The updated predictor was used to assess the specificities of HLA-C molecules, which were found to cover a more limited sequence space than HLA-A and -B molecules. Assessing the functional significance of these new tools, HLA-C*07:01 transgenic mice were immunized with stable HLA-C*07:01 binders; six of six tested stable peptide binders were immunogenic. Finally, we generated HLA-C tetramers and labeled human CD8+ T cells and NK cells. These new resources should support future research on the biology of HLA-C molecules. The data are deposited at the Immune Epitope Database, and the updated NetMHCpan predictor is available at the Center for Biological Sequence Analysis and the Immune Epitope Database.
Fil: Rasmussen, Michael. Universidad de Copenhagen; Dinamarca
Fil: Harndahl, Mikkel. Universidad de Copenhagen; Dinamarca
Fil: Stryhn, Anette. Universidad de Copenhagen; Dinamarca
Fil: Boucherma, Rachid. Inserm; Francia. Groupe Hospitalier Cochin-Port-Royal; Francia
Fil: Nielsen, Lise Lotte. Universidad de Copenhagen; Dinamarca
Fil: Lemonnier, François A.. Inserm; Francia. Groupe Hospitalier Cochin-Port-Royal; Francia
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: Buus, Søren. Universidad de Copenhagen; Dinamarca
Materia
MHC
Binding specificity
HLA-C
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:11336/18026
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/18026
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Uncovering the peptide-binding specificities of HLA-C: a general strategy to determine the specificity of any MHC class I moleculeRasmussen, MichaelHarndahl, MikkelStryhn, AnetteBoucherma, RachidNielsen, Lise LotteLemonnier, François A.Nielsen, MortenBuus, SørenMHCBinding specificityHLA-Chttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3MHC class I molecules (HLA-I in humans) present peptides derived from endogenous proteins to CTLs. Whereas the peptide-binding specificities of HLA-A and -B molecules have been studied extensively, little is known about HLA-C specificities. Combining a positional scanning combinatorial peptide library approach with a peptide–HLA-I dissociation assay, in this study we present a general strategy to determine the peptide-binding specificity of any MHC class I molecule. We applied this novel strategy to 17 of the most common HLA-C molecules, and for 16 of these we successfully generated matrices representing their peptide-binding motifs. The motifs prominently shared a conserved C-terminal primary anchor with hydrophobic amino acid residues, as well as one or more diverse primary and auxiliary anchors at P1, P2, P3, and/or P7. Matrices were used to generate a large panel of HLA-C–specific peptide-binding data and update our pan-specific NetMHCpan predictor, whose predictive performance was considerably improved with respect to peptide binding to HLA-C. The updated predictor was used to assess the specificities of HLA-C molecules, which were found to cover a more limited sequence space than HLA-A and -B molecules. Assessing the functional significance of these new tools, HLA-C*07:01 transgenic mice were immunized with stable HLA-C*07:01 binders; six of six tested stable peptide binders were immunogenic. Finally, we generated HLA-C tetramers and labeled human CD8+ T cells and NK cells. These new resources should support future research on the biology of HLA-C molecules. The data are deposited at the Immune Epitope Database, and the updated NetMHCpan predictor is available at the Center for Biological Sequence Analysis and the Immune Epitope Database.Fil: Rasmussen, Michael. Universidad de Copenhagen; DinamarcaFil: Harndahl, Mikkel. Universidad de Copenhagen; DinamarcaFil: Stryhn, Anette. Universidad de Copenhagen; DinamarcaFil: Boucherma, Rachid. Inserm; Francia. Groupe Hospitalier Cochin-Port-Royal; FranciaFil: Nielsen, Lise Lotte. Universidad de Copenhagen; DinamarcaFil: Lemonnier, François A.. Inserm; Francia. Groupe Hospitalier Cochin-Port-Royal; FranciaFil: 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: Buus, Søren. Universidad de Copenhagen; DinamarcaAmer Assoc Immunologists2014-11info: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/11336/18026Rasmussen, Michael; Harndahl, Mikkel; Stryhn, Anette; Boucherma, Rachid; Nielsen, Lise Lotte; et al.; Uncovering the peptide-binding specificities of HLA-C: a general strategy to determine the specificity of any MHC class I molecule; Amer Assoc Immunologists; Journal Of Immunology; 193; 10; 11-2014; 4790-48020022-17671550-6606enginfo:eu-repo/semantics/altIdentifier/url/http://www.jimmunol.org/content/193/10/4790.longinfo:eu-repo/semantics/altIdentifier/doi/10.4049/jimmunol.1401689info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4226424/info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:51:19Zoai:ri.conicet.gov.ar:11336/18026instacron: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 09:51:19.512CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Uncovering the peptide-binding specificities of HLA-C: a general strategy to determine the specificity of any MHC class I molecule
title Uncovering the peptide-binding specificities of HLA-C: a general strategy to determine the specificity of any MHC class I molecule
spellingShingle Uncovering the peptide-binding specificities of HLA-C: a general strategy to determine the specificity of any MHC class I molecule
Rasmussen, Michael
MHC
Binding specificity
HLA-C
title_short Uncovering the peptide-binding specificities of HLA-C: a general strategy to determine the specificity of any MHC class I molecule
title_full Uncovering the peptide-binding specificities of HLA-C: a general strategy to determine the specificity of any MHC class I molecule
title_fullStr Uncovering the peptide-binding specificities of HLA-C: a general strategy to determine the specificity of any MHC class I molecule
title_full_unstemmed Uncovering the peptide-binding specificities of HLA-C: a general strategy to determine the specificity of any MHC class I molecule
title_sort Uncovering the peptide-binding specificities of HLA-C: a general strategy to determine the specificity of any MHC class I molecule
dc.creator.none.fl_str_mv Rasmussen, Michael
Harndahl, Mikkel
Stryhn, Anette
Boucherma, Rachid
Nielsen, Lise Lotte
Lemonnier, François A.
Nielsen, Morten
Buus, Søren
author Rasmussen, Michael
author_facet Rasmussen, Michael
Harndahl, Mikkel
Stryhn, Anette
Boucherma, Rachid
Nielsen, Lise Lotte
Lemonnier, François A.
Nielsen, Morten
Buus, Søren
author_role author
author2 Harndahl, Mikkel
Stryhn, Anette
Boucherma, Rachid
Nielsen, Lise Lotte
Lemonnier, François A.
Nielsen, Morten
Buus, Søren
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv MHC
Binding specificity
HLA-C
topic MHC
Binding specificity
HLA-C
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv MHC class I molecules (HLA-I in humans) present peptides derived from endogenous proteins to CTLs. Whereas the peptide-binding specificities of HLA-A and -B molecules have been studied extensively, little is known about HLA-C specificities. Combining a positional scanning combinatorial peptide library approach with a peptide–HLA-I dissociation assay, in this study we present a general strategy to determine the peptide-binding specificity of any MHC class I molecule. We applied this novel strategy to 17 of the most common HLA-C molecules, and for 16 of these we successfully generated matrices representing their peptide-binding motifs. The motifs prominently shared a conserved C-terminal primary anchor with hydrophobic amino acid residues, as well as one or more diverse primary and auxiliary anchors at P1, P2, P3, and/or P7. Matrices were used to generate a large panel of HLA-C–specific peptide-binding data and update our pan-specific NetMHCpan predictor, whose predictive performance was considerably improved with respect to peptide binding to HLA-C. The updated predictor was used to assess the specificities of HLA-C molecules, which were found to cover a more limited sequence space than HLA-A and -B molecules. Assessing the functional significance of these new tools, HLA-C*07:01 transgenic mice were immunized with stable HLA-C*07:01 binders; six of six tested stable peptide binders were immunogenic. Finally, we generated HLA-C tetramers and labeled human CD8+ T cells and NK cells. These new resources should support future research on the biology of HLA-C molecules. The data are deposited at the Immune Epitope Database, and the updated NetMHCpan predictor is available at the Center for Biological Sequence Analysis and the Immune Epitope Database.
Fil: Rasmussen, Michael. Universidad de Copenhagen; Dinamarca
Fil: Harndahl, Mikkel. Universidad de Copenhagen; Dinamarca
Fil: Stryhn, Anette. Universidad de Copenhagen; Dinamarca
Fil: Boucherma, Rachid. Inserm; Francia. Groupe Hospitalier Cochin-Port-Royal; Francia
Fil: Nielsen, Lise Lotte. Universidad de Copenhagen; Dinamarca
Fil: Lemonnier, François A.. Inserm; Francia. Groupe Hospitalier Cochin-Port-Royal; Francia
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: Buus, Søren. Universidad de Copenhagen; Dinamarca
description MHC class I molecules (HLA-I in humans) present peptides derived from endogenous proteins to CTLs. Whereas the peptide-binding specificities of HLA-A and -B molecules have been studied extensively, little is known about HLA-C specificities. Combining a positional scanning combinatorial peptide library approach with a peptide–HLA-I dissociation assay, in this study we present a general strategy to determine the peptide-binding specificity of any MHC class I molecule. We applied this novel strategy to 17 of the most common HLA-C molecules, and for 16 of these we successfully generated matrices representing their peptide-binding motifs. The motifs prominently shared a conserved C-terminal primary anchor with hydrophobic amino acid residues, as well as one or more diverse primary and auxiliary anchors at P1, P2, P3, and/or P7. Matrices were used to generate a large panel of HLA-C–specific peptide-binding data and update our pan-specific NetMHCpan predictor, whose predictive performance was considerably improved with respect to peptide binding to HLA-C. The updated predictor was used to assess the specificities of HLA-C molecules, which were found to cover a more limited sequence space than HLA-A and -B molecules. Assessing the functional significance of these new tools, HLA-C*07:01 transgenic mice were immunized with stable HLA-C*07:01 binders; six of six tested stable peptide binders were immunogenic. Finally, we generated HLA-C tetramers and labeled human CD8+ T cells and NK cells. These new resources should support future research on the biology of HLA-C molecules. The data are deposited at the Immune Epitope Database, and the updated NetMHCpan predictor is available at the Center for Biological Sequence Analysis and the Immune Epitope Database.
publishDate 2014
dc.date.none.fl_str_mv 2014-11
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/11336/18026
Rasmussen, Michael; Harndahl, Mikkel; Stryhn, Anette; Boucherma, Rachid; Nielsen, Lise Lotte; et al.; Uncovering the peptide-binding specificities of HLA-C: a general strategy to determine the specificity of any MHC class I molecule; Amer Assoc Immunologists; Journal Of Immunology; 193; 10; 11-2014; 4790-4802
0022-1767
1550-6606
url http://hdl.handle.net/11336/18026
identifier_str_mv Rasmussen, Michael; Harndahl, Mikkel; Stryhn, Anette; Boucherma, Rachid; Nielsen, Lise Lotte; et al.; Uncovering the peptide-binding specificities of HLA-C: a general strategy to determine the specificity of any MHC class I molecule; Amer Assoc Immunologists; Journal Of Immunology; 193; 10; 11-2014; 4790-4802
0022-1767
1550-6606
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://www.jimmunol.org/content/193/10/4790.long
info:eu-repo/semantics/altIdentifier/doi/10.4049/jimmunol.1401689
info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4226424/
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 Amer Assoc Immunologists
publisher.none.fl_str_mv Amer Assoc Immunologists
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_ 1842269088183746560
score 13.13397

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