학술논문
SARS-CoV-2 spike protein-derived immunogenic peptides that are promiscuously presented by several HLA-class II molecules and their potential for inducing acquired immunity.
Document Type
Academic Journal
Author
Yajima Y; Department of Oral and Maxillofacial Surgery, Asahikawa Medical University, Asahikawa, Hokkaido, Japan.; Department of Pathology, Asahikawa Medical University, Asahikawa, Hokkaido, Japan.; Kosaka A; Department of Pathology, Asahikawa Medical University, Asahikawa, Hokkaido, Japan.; Ohkuri T; Department of Pathology, Asahikawa Medical University, Asahikawa, Hokkaido, Japan.; Hirohashi Y; Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan.; Li D; Tsukuba Laboratory, Medical & Biological Laboratories Co., Ltd., Ina, Japan.; Nagasaki T; Tsukuba Laboratory, Medical & Biological Laboratories Co., Ltd., Ina, Japan.; Nagato T; Department of Pathology, Asahikawa Medical University, Asahikawa, Hokkaido, Japan.; Torigoe T; Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan.; Kobayashi H; Department of Pathology, Asahikawa Medical University, Asahikawa, Hokkaido, Japan.
Source
Publisher: Elsevier Ltd Country of Publication: England NLM ID: 101672560 Publication Model: eCollection Cited Medium: Print ISSN: 2405-8440 (Print) Linking ISSN: 24058440 NLM ISO Abbreviation: Heliyon Subsets: PubMed not MEDLINE
Subject
Language
English
ISSN
2405-8440
Abstract
The current coronavirus disease 2019 (COVID-19) pandemic that is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has a significant threat to public health. Although vaccines based on the mRNA of the SARS-CoV-2 spike protein have been developed to induce both cellular and humoral immunity against SARS-CoV-2, there have been some concerns raised about their high cost, particularly in developing countries. In the present study, we aim to identify an immunogenic peptide in the SARS-CoV-2 spike protein to activate cellular immunity, particularly CD4 + helper T lymphocytes (Th cells), which are a commander of immune system. SARS-CoV-2 spike protein-derived peptides Spike 448-477 and Spike 489-513(N501Y) -specific CD4 + Th cell lines were generated by repetitive stimulation of healthy donor-derived CD4 + T-cells with each peptide. Their HLA-restrictions were addressed by using blocking antibodies against HLA and HLA-transfected L-cells. The epitopes of Spike 448-477 -specific CD4 + Th cell lines were defined using a series of 7-14-mer overlapping truncated peptides and alanine-substituted epitope peptides. To address responsiveness of these CD4 + Th cell lines to several SARS-CoV-2 variants, we stimulated the CD4 + Th cell lines with mutated peptides. We addressed whether these identified peptides were useful for monitoring T-cell-based immune responses in vaccinated donors using the IFN-γ ELISpot assay. The Spike 448-477 peptide was found to be a promiscuous peptide presented by HLA- DRB1*08:02, DR53, and DPB1*02:02. Although HLA-DPB1*02:02-restricted CD4 + Th cells did not response to some peptides with the L452R and L452Q mutations, the other CD4 + Th cells were not affected by any mutant peptides. We developed two tetramers to detect HLA-DRB1*08:02/Spike 449-463 - and Spike 449-463 (L452R/Y453F)-recognizing CD4 + Th cells. Spike 489-513(N501Y) peptide was also a promiscuously presented to HLA-DRB1*09:01 and DRB1*15:02. The T-cell responses specific to both peptides Spike 448-477 and Spike 489-513 were detected in PBMCs after vaccinations. In addition, we observed that the Spike 448-477 peptide activated both CD8 + T-cells and CD4 + Th cells in individuals receiving mRNA vaccines. SARS-CoV-2 spike protein-derived peptides, Spike 448-477 and Spike 489-513 , include several epitopes that are presented by multiple HLA-class II alleles to activate CD4 + Th cells, which are considered useful for monitoring the establishment of acquired immunity after vaccination.
Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Hiroya Kobayashi has been provided with all peptides and tetramers from Medical & Biological Laboratories Co., Ltd.Co-authors currently employed by Medical & Biological Laboratories Co., Ltd.-Li D, and Nagasaki T.
(© 2023 The Authors.)
Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Hiroya Kobayashi has been provided with all peptides and tetramers from Medical & Biological Laboratories Co., Ltd.Co-authors currently employed by Medical & Biological Laboratories Co., Ltd.-Li D, and Nagasaki T.
(© 2023 The Authors.)