Abstract
We studied SARS-CoV-2-specific T cell responses in 22 subacute MIS-C children enrolled in 2021 and 2022 using peptide pools derived from SARS-CoV-2 spike or nonspike proteins. CD4+ and CD8+ SARS-CoV-2-specific T cells were detected in 5 subjects, CD4+ T helper (Th) responses alone were detected in 12 subjects, and CD8+ cytotoxic T cell (CTL) responses alone were documented in 1 subject. Notably, a sizeable subpopulation of CD4- CD8- double-negative (DN) T cells out of total CD3+ T cells was observed in MIS-C (median: 14.5%; IQR 8.65-25.3) and recognized SARS-CoV-2 peptides. T cells bearing the Vβ21.3 T cell receptor (TcRs), previously reported as pathogenic in the context of MIS-C, were detected in high frequencies, namely, in 2.8% and 3.9% of the CD4+ and CD8+ T cells, respectively. However, Vβ21.3 CD8+ T cells that responded to SARS-CoV-2 peptides were detected in only a single subject, suggesting recognition of nonviral antigens in the majority of subjects. Subjects studied 6-14 months after MIS-C showed T cell epitope spreading, meaning the activation of T cells that recognize more SARS-CoV-2 peptides following the initial expansion of T cells that see immunodominant epitopes. For example, subjects that did not recognize nonspike proteins in the subacute phase of MIS-C showed good Th response to nonspike peptides, and/or CD8+ T cell responses not appreciable before arose over time and could be detected in the 6-14 months’ follow-up. The magnitude of the Th and CTL responses also increased over time. In summary, patients with MIS-C associated with acute lymphopenia, a classical feature of MIS-C, showed a physiological response to the virus with a prominent role for virus-specific DN T cells.
Keywords: CD4− CD8− double-negative T cells; MIS-C; SARS-CoV-2; T cell receptor Vβ21.3; T cells.
【저자키워드】 SARS-CoV-2, MIS-C, T cells., CD4− CD8− double-negative T cells, T cell receptor Vβ21.3, 【초록키워드】 T cells, children, peptide, CD8+ T cells, Proteins, SARS-CoV-2 peptides, virus, CD4, CD8, MIS-C, Antigen, lymphopenia, Protein, Epitopes, T cell, response, T cell responses, Patient, peptides, Follow-up, epitope, T cell receptor, T cell response, CTL, CD8+ T cell, immunodominant epitopes, SARS-CoV-2-specific T cells, SARS-CoV-2 spike, Cytotoxic T cell, T helper, Activation, Recognition, frequencies, subject, CD4+, pathogenic, single subject, CD8+, peptide pools, physiological response, subpopulation, CD3+, TCRs, initial, enrolled, classical, example, reported, majority, subjects, recognize, magnitude, IQR, peptide pool, SARS-CoV-2 peptide, SARS-CoV-2-specific T cell, 【제목키워드】 CD4, CD8, response, helper, Numerous,