Screening for immunodominant epitopes of SARS-CoV-2 based on CD8⁺ T cell responses from individuals with HLA-A homozygous alleles.

IF 3.2 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular immunology Pub Date : 2025-01-25 DOI:10.1016/j.molimm.2025.01.010

Rui He, Lingxin Meng, Yuting Sun, Jingsong Wang, Shufeng Wang, Yueping Liu, Lei Fei, Zhongfang Wang, Qinggao Zhang, Yuzhang Wu, Yongwen Chen, Bo Diao

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引用次数: 0

Abstract

Purpose: SARS-CoV-2-specific CD8⁺ cytotoxic T lymphocytes (CTLs) are crucial in viral clearance, disease progression, and reinfection control. However, numerous SARS-CoV-2 immunodominant CTL epitopes theoretically are still unidentified due to the genetic polymorphism of human leukocyte antigen class I (HLA-I) molecules.

Methods: The CTL epitopes of SARS-CoV-2 were predicted by the epitope affinity and immunogenicity prediction platforms: the NetMHCpan and the PromPPD. Individuals with HLA-A homozygous alleles were screened from 252 COVID-19 vaccinees, including the Ad5-nCoV vaccine (CanSino, n = 183) and the CoronaVac inactivated vaccine (Sinovac, n = 69) using MiSeqDx™ generation sequencing, and their PBMCs were further stimulated by the predicted peptides to screen the immunodominant epitopes according to the secretion of IFN-γ from CD8⁺ T cells. Peptide-MHC tetramers were constructed and used to detect the frequency of antigen specific CTLs in vivo.

Results: Individuals with HLA-A homozygous alleles including HLA-A*01 (n = 1), -A*02 (n = 9), - A*03 and -A*11 (n = 12), and -A*24 (n = 7) supertypes were selected. Twelve immunodominant CTL epitopes for these HLA-A allotypes were finally screened based on the frequency of IFN-γ⁺CD8⁺ T cells in homozygous individuals. The SARS-CoV-2 specific CTLs from Omicron variant infected patients were successfully evaluated by these novel peptide-HLA tetramers.

Conclusion: A set of immunodominant CTL epitopes of SARS-CoV-2 was identified, and the antigen-specific CD8⁺ T cells in viral infected patients or COVID-19 vaccinees could be rapidly detected by a mixture of the peptide-MHC tetramers.

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来源期刊

Molecular immunology 医学-免疫学

CiteScore

6.90

自引率

2.80%

发文量

324

审稿时长

50 days

期刊介绍： Molecular Immunology publishes original articles, reviews and commentaries on all areas of immunology, with a particular focus on description of cellular, biochemical or genetic mechanisms underlying immunological phenomena. Studies on all model organisms, from invertebrates to humans, are suitable. Examples include, but are not restricted to: Infection, autoimmunity, transplantation, immunodeficiencies, inflammation and tumor immunology Mechanisms of induction, regulation and termination of innate and adaptive immunity Intercellular communication, cooperation and regulation Intracellular mechanisms of immunity (endocytosis, protein trafficking, pathogen recognition, antigen presentation, etc) Mechanisms of action of the cells and molecules of the immune system Structural analysis Development of the immune system Comparative immunology and evolution of the immune system "Omics" studies and bioinformatics Vaccines, biotechnology and therapeutic manipulation of the immune system (therapeutic antibodies, cytokines, cellular therapies, etc) Technical developments.