In silico and in vitro arboviral MHC class I-restricted-epitope signatures reveal immunodominance and poor overlapping patterns

• DOI: 10.3389/fimmu.2022.1035515
• Publication Date: 2022-11-17T07:40:51Z
• Authors: Ágata Lopes-Ribeiro; Franklin Pereira ...; Patrícia de Melo ...; Lorena de Almeida...; Geovane Marques F...; Alice Aparecida L...; Laura Cardoso Cor...; Caio Wilker Teixeira; Henrique Morais R...; Élisson Nogueira ...; Alice Freitas Ver...; Edel Figueiredo B...; Flávio Guimarães ...; Olindo Assis Mart...; Moriya Tsuji; Vanessa Peruhype-...; Jordana Grazziela...
• Keywords: Flavivirus; Reverse vaccinology

Introduction The present work sought to identify MHC-I-restricted peptide signatures for arbovirus using in silico and vitro microarray tools. Methods First, an in-silico analysis of immunogenic epitopes restricted four the most prevalent human MHC class-I was performed by identification affinity score. For that, more than 10,000 sequences from 5 Arbovirus 8 different viral serotypes, namely Zika (ZIKV), Dengue (DENV serotypes 1-4), Chikungunya (CHIKV), Mayaro (MAYV) Oropouche (OROV) viruses, addition YFV were analyzed. Haplotype HLA-A*02.01 dominant all arboviruses. Over one thousand HLA-A2 peptides employed build a comprehensive identity matrix. Intending assess HLAA*02:01 reactivity vitro, designed generated dimeric protein containing HLA-A*02:01. Results matrix allowed only three overlapping between two or flavivirus sequences, suggesting poor virus-specific amongst arborviruses. Global fluorescence intensity peptide-HLA-A*02:01 binding indicated dose-dependent effect array. Considering assessed arboviruses, number DENV-derived with HLA-A*02:01 highest. Furthermore, lower YFV-17DD presented when compared non-overlapping peptides. In addition, assessment HLA-A*02:01-reactive across virus polyproteins highlighted non-structural proteins as “hot-spots”. Data supported these findings showing presence major hydrophobic sites final segment 1 throughout 2a (Ns2a) nonstructural 2b (Ns2b), 4a (Ns4a) 4b (Ns4b). Discussion To our knowledge, results provide detailed snapshot immunodominant signature MHC-class I restriction, which may bring insight into design future vaccines arboviruses vaccination protocols highly endemic areas.