Integrating in silico and in vitro analysis of peptide binding affinity to HLA-Cw*0102: a bioinformatic approach to the prediction of new epitopes
| العنوان: | Integrating in silico and in vitro analysis of peptide binding affinity to HLA-Cw*0102: a bioinformatic approach to the prediction of new epitopes |
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| المؤلفون: | Ian Williams, Frans H.J. Claas, Arend Mulder, Irini Doytchinova, Pierre Pellegrino, Emma L. Turnbull, MaiLee Wong, Valerie Walshe, Persephone Borrow, Darren R. Flower, Isabel K. Macdonald, Jo Turner, Channa K. Hattotuwagama |
| المصدر: | PLoS ONE PLoS ONE, Vol 4, Iss 11, p e8095 (2009) |
| سنة النشر: | 2009 |
| مصطلحات موضوعية: | In silico, Amino Acid Motifs, lcsh:Medicine, Peptide binding, Plasma protein binding, Computational biology, Human leukocyte antigen, HLA-C Antigens, In Vitro Techniques, Major histocompatibility complex, Bioinformatics, Epitope, Major Histocompatibility Complex, 03 medical and health sciences, Epitopes, 0302 clinical medicine, MHC class I, Humans, lcsh:Science, Alleles, Edetic Acid, Virology/Vaccines, 030304 developmental biology, 0303 health sciences, Multidisciplinary, Models, Statistical, biology, lcsh:R, MHC Class I Gene, Histocompatibility Antigens Class I, Computational Biology, 3. Good health, Protein Structure, Tertiary, Immunology/Immune Response, biology.protein, HIV-1, Leukocytes, Mononuclear, Immunology/Antigen Processing and Recognition, lcsh:Q, Peptides, 030215 immunology, Protein Binding, Research Article |
| الوصف: | BACKGROUND: Predictive models of peptide-Major Histocompatibility Complex (MHC) binding affinity are important components of modern computational immunovaccinology. Here, we describe the development and deployment of a reliable peptide-binding prediction method for a previously poorly-characterized human MHC class I allele, HLA-Cw*0102. METHODOLOGY/FINDINGS: Using an in-house, flow cytometry-based MHC stabilization assay we generated novel peptide binding data, from which we derived a precise two-dimensional quantitative structure-activity relationship (2D-QSAR) binding model. This allowed us to explore the peptide specificity of HLA-Cw*0102 molecule in detail. We used this model to design peptides optimized for HLA-Cw*0102-binding. Experimental analysis showed these peptides to have high binding affinities for the HLA-Cw*0102 molecule. As a functional validation of our approach, we also predicted HLA-Cw*0102-binding peptides within the HIV-1 genome, identifying a set of potent binding peptides. The most affine of these binding peptides was subsequently determined to be an epitope recognized in a subset of HLA-Cw*0102-positive individuals chronically infected with HIV-1. CONCLUSIONS/SIGNIFICANCE: A functionally-validated in silico-in vitro approach to the reliable and efficient prediction of peptide binding to a previously uncharacterized human MHC allele HLA-Cw*0102 was developed. This technique is generally applicable to all T cell epitope identification problems in immunology and vaccinology. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1932-6203 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3e2bacf2ec058a8349730659a4471119 http://ora.ox.ac.uk/objects/uuid:4be60774-61de-45cf-8df9-58aca66ff937 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....3e2bacf2ec058a8349730659a4471119 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19326203 |
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