Artículo
Uncovering the peptide-binding specificities of HLA-C: a general strategy to determine the specificity of any MHC class I molecule
Rasmussen, Michael; Harndahl, Mikkel; Stryhn, Anette; Boucherma, Rachid; Nielsen, Lise Lotte; Lemonnier, François A.; Nielsen, Morten
; Buus, Søren
Fecha de publicación:
11/2014
Editorial:
Amer Assoc Immunologists
Revista:
Journal Of Immunology
ISSN:
0022-1767
e-ISSN:
1550-6606
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
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.
Palabras clave:
Mhc
,
Binding Specificity
,
Hla-C
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Colecciones
Articulos(IIB)
Articulos de INSTITUTO DE INVESTIGACIONES BIOLOGICAS
Articulos de INSTITUTO DE INVESTIGACIONES BIOLOGICAS
Articulos(IQUIFIB)
Articulos de INST.DE QUIMICA Y FISICO-QUIMICA BIOLOGICAS "PROF. ALEJANDRO C. PALADINI"
Articulos de INST.DE QUIMICA Y FISICO-QUIMICA BIOLOGICAS "PROF. ALEJANDRO C. PALADINI"
Citación
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
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