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

Ágata Lopes-Ribeiro, Franklin Pereira Araujo, Patrícia de Melo Oliveira, Lorena de Almeida Teixeira, Geovane Marques Ferreira, Alice Aparecida Lourenço, Laura Cardoso Corrêa Dias, Caio Wilker Teixeira, Henrique Morais Retes, Élisson Nogueira Lopes, Alice Freitas Versiani, Edel Figueiredo Barbosa-Stancioli, Flávio Guimarães da Fonseca, Olindo Assis Martins-Filho, Moriya Tsuji, Vanessa Peruhype-Magalhães, Jordana Grazziela Alves Coelho-dos-Reis

Research output: Contribution to journalArticlepeer-review

Abstract

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

Original languageEnglish (US)
Article number1035515
JournalFrontiers in immunology
Volume13
DOIs
StatePublished - Nov 17 2022

Keywords

  • CD8T cell response
  • HLA-A2-restricted peptides
  • MHC-I peptides
  • arbovirus
  • immunoinformatics
  • overlapping peptides

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Fingerprint

Dive into the research topics of 'In silico and in vitro arboviral MHC class I-restricted-epitope signatures reveal immunodominance and poor overlapping patterns'. Together they form a unique fingerprint.

Cite this