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dc.contributor.author
Rasmussen, Michael
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dc.contributor.author
Harndahl, Mikkel
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dc.contributor.author
Stryhn, Anette
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dc.contributor.author
Boucherma, Rachid
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dc.contributor.author
Nielsen, Lise Lotte
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dc.contributor.author
Lemonnier, François A.
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dc.contributor.author
Nielsen, Morten
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dc.contributor.author
Buus, Søren
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dc.date.available
2017-06-12T20:13:49Z
dc.date.issued
2014-11
dc.identifier.citation
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
dc.identifier.issn
0022-1767
dc.identifier.uri
http://hdl.handle.net/11336/18026
dc.description.abstract
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.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Amer Assoc Immunologists
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dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
Mhc
dc.subject
Binding Specificity
dc.subject
Hla-C
dc.subject.classification
Otras Medicina Básica
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dc.subject.classification
Medicina Básica
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dc.subject.classification
CIENCIAS MÉDICAS Y DE LA SALUD
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dc.title
Uncovering the peptide-binding specificities of HLA-C: a general strategy to determine the specificity of any MHC class I molecule
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2017-06-09T15:01:07Z
dc.identifier.eissn
1550-6606
dc.journal.volume
193
dc.journal.number
10
dc.journal.pagination
4790-4802
dc.journal.pais
Estados Unidos
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dc.journal.ciudad
Bethesda
dc.description.fil
Fil: Rasmussen, Michael. Universidad de Copenhagen; Dinamarca
dc.description.fil
Fil: Harndahl, Mikkel. Universidad de Copenhagen; Dinamarca
dc.description.fil
Fil: Stryhn, Anette. Universidad de Copenhagen; Dinamarca
dc.description.fil
Fil: Boucherma, Rachid. Inserm; Francia. Groupe Hospitalier Cochin-Port-Royal; Francia
dc.description.fil
Fil: Nielsen, Lise Lotte. Universidad de Copenhagen; Dinamarca
dc.description.fil
Fil: Lemonnier, François A.. Inserm; Francia. Groupe Hospitalier Cochin-Port-Royal; Francia
dc.description.fil
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
dc.description.fil
Fil: Buus, Søren. Universidad de Copenhagen; Dinamarca
dc.journal.title
Journal Of Immunology
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dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/http://www.jimmunol.org/content/193/10/4790.long
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.4049/jimmunol.1401689
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4226424/
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