In silico analyses and experimental validation of the MHC class-I restricted epitopes of Ebolavirus GP

Author:

Liu Yang12,Sun Baozeng1,Wang Jiawei1,Sun Hao13,Lu Zhenhua4,Chen Longyu1,Lan Mingfu1,Xu Jiahao1,Pan Jingyu1,Shi Jingqi1,Sun Yuanjie1,Zhang Xiyang1,Wang Jing1,Jiang Dongbo1ORCID,Yang Kun1

Affiliation:

1. Department of Immunology, Basic Medicine School, Air-Force Medical University (the Fourth Military Medical University) , Xi’an, Shaanxi, 86-710032 , P.R. China

2. Institute of AIDS Prevention and Control,Shaanxi Provincial Center for Disease Control and Prevention , Xi’an, Shaanxi, 86-710054 , P.R. China

3. Department of Internal Medicine, Tangshan Sannvhe Airport Hospital , Tangshan, Hebei, 86-063000 , P.R. China

4. Department of Epidemiology, Public Health School, Air-Force Medical University (the Fourth Military Medical University) , Xi’an, Shaanxi, 86-710032 , P.R. China

Abstract

Abstract Ebolavirus (EBOV) causes an extremely high mortality and prevalence disease called Ebola virus disease (EVD). There is only one glycoprotein (GP) on the virus particle surface, which mediates entry into the host cell. Major histocompatibility complex (MHC) class-I restricted cluster of differentiation 8 (CD8+) T cell responses are important antiviral immune responses. Therefore, it is of great importance to understand EBOV GP-specific MHC class-I restricted epitopes within immunogenicity. In this study, computational approaches were employed to predict the dominant MHC class-I molecule epitopes of EBOV GP for mouse H2 and major alleles of human leukocyte antigen (HLA) class-I supertypes. Our results yielded 42 dominant epitopes in H2 haplotypes and 301 dominant epitopes in HLA class-I haplotypes. After validation by enzyme-linked immunospot (ELISpot) assay, in-depth analyses to ascertain their nature of conservation, immunogenicity, and docking with the corresponding MHC class-I molecules were undertaken. Our study predicted MHC class-I restricted epitopes that may aid the advancement of anti-EBOV immune responses. An integrated strategy of epitope prediction, validation and comparative analyses was postulated, which is promising for epitope-based immunotherapy development and application to viral epidemics.

Funder

National Natural Science Foundation of China

Key Research and Development Program of Shaanxi Province

Natural Science Basic Research Program of Shaanxi Province

Publisher

Oxford University Press (OUP)

Subject

Immunology,General Medicine,Immunology and Allergy

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