Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has developed variants escaping neutralization antibody immunity established against the original virus. An understanding of broad-spectrum adaptive immunity, including CD8 + T cell immunity to wide range of epitopes, could help translational efforts to improve coronavirus disease 2019 (COVID-19) prevention and therapy. However, there have been few direct studies in which such immunity exists in a population. Methods: We selected SARS-CoV-2-conserved structural peptides that are not prone to mutation as antigens for broad-spectrum CD8 + T cell immunity. Peripheral blood mononuclear cells (PBMCs) from unexposed healthy donors were stimulated with these peptides in vitro and CD8 + T cell-specific response was monitored. The conserved peptide-specific CD8 + T cells were sorted for T cell receptor (TCR) repertoire sequencing. The presence of specific complementary determining region 3 (CDR3) clones was analyzed in a healthy cohort. Results: For each structural protein, including S, E, M, N, the conserved peptides could potentially provide the largest number of major histocompatibility complex-I (MHC-I) epitopes in the Oriental and Caucasian populations. For conserved peptides from spike (S), envelope (E), membrane (M), nucleocapsid (N) proteins, we found that there were no cross-reactive memory T cells in the unexposed individuals. Instead, their T cells contain naïve TCR repertoire recognizing these conserved peptides. Using TCR sequencing and CDR3 clustering for the conserved peptides specific T cells, we found that the recovered patients had a higher proportion of TCR repertoire similar with that of specific CD8 + T cells in unexposed individuals. Meanwhile, CDR3 clones of the above T cells were widely present in the healthy population. Conclusions: This study provides evidence of broad-spectrum SARS-CoV-2 specific CD8 + TCR repertoire in unexposed healthy population, which is implicated in the development and implementation of broad-spectrum vaccines against COVID-19.
【저자키워드】 SARS-CoV-2, Vaccine, TCR repertoire, broad-spectrum adaptive immunity, CD8+ T cell, 【초록키워드】 COVID-19, coronavirus disease, coronavirus, therapy, Mutation, adaptive, Immunity, T cells, neutralization, Sequencing, variant, peptide, Proteins, in vitro, virus, CD8, Antigen, Protein, Epitopes, Cohort, T cell, nucleocapsid, implementation, Clustering, peptides, membrane, epitope, TCR, T cell receptor, memory T cell, Blood, Evidence, PBMCs, complementary, cross-reactive, TCR sequencing, MHC-I, mononuclear cell, acute respiratory syndrome, help, naïve, effort, antibody immunity, clone, CDR3, peripheral, populations, healthy donor, IMPROVE, recovered patient, stimulated, selected, analyzed, conserved, proportion, healthy, provide, recognizing, individuals, implicated, translational, the healthy, 【제목키워드】 CD8, TCR, repertoire, Specific,