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• W793398751 abstract "Cytotoxic T-lymphocytes (CTLs) are the key players of adaptive cellular immunity, being able to identify and eliminate infected cells through the interaction with peptide-loaded major histocompatibility complexes class I (pMHC-I). Despite the high specificity of this interaction, a given lymphocyte is actually able to recognize more than just one pMHC-I complex, a phenomenon referred as cross-reactivity. In the present work we describe the use of pMHC-I structural features as input for multivariate statistical methods, to perform standardized structure-based predictions of cross-reactivity among viral epitopes. Our improved approach was able to successfully identify cross-reactive targets among 28 naturally occurring hepatitis C virus (HCV) variants and among eight epitopes from the four dengue virus serotypes. In both cases, our results were supported by multiscale bootstrap resampling and by data from previously published in vitro experiments. The combined use of data from charges and accessible surface area (ASA) of selected residues over the pMHC-I surface provided a powerful way of assessing the structural features involved in triggering cross-reactive responses. Moreover, the use of an R package (pvclust) for assessing the uncertainty in the hierarchical cluster analysis provided a statistical support for the interpretation of results. Taken together, these methods can be applied to vaccine design, both for the selection of candidates capable of inducing immunity against different targets, or to identify epitopes that could trigger undesired immunological responses." @default.
• W793398751 created "2016-06-24" @default.
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• W793398751 date "2015-10-01" @default.
• W793398751 modified "2023-10-16" @default.
• W793398751 title "Improved structural method for T-cell cross-reactivity prediction" @default.
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• W793398751 doi "https://doi.org/10.1016/j.molimm.2015.06.017" @default.
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