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. 2022 Jun 29;23(13):7219. doi: 10.3390/ijms23137219

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© 2022 by the authors.

Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).

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T cell responses to peptide megapools derived from SARS-CoV-2 in MIS-C subjects healthy 6-14 months after the disease onset. Six MIS-C subjects (2, 3, 5, 12, 14, and 16) studied at their subacute phase were also studied 6–14 months later. Canonical CD4+ and CD8+, CD4− CD8− DN, and TCR Vβ21.3+ CD4+ and CD8+ T cell responses to SARS-CoV-2 peptide megapools were studied. The SI of AIM+ T cells from each individual subject was calculated to study the T cell responses. (A) CD4+ and CD8+ T cell responses to peptide megapools and their CCR6 expressions. Three subjects (2, 3, and 5) of the 6 subjects showed concurrent CD4+ and CD8+ T cell responses, and the other 3 follow-up MIS-C subjects (12, 14, and 16) showed only CD4+ T cell responses to SARS-CoV-2 (both CD4 spike (S) and nonspike (R) megapools). (B) Memory phenotypes of AIM+ CD4+ (left panels) and CD8+ (right panels) T cells. Red circles: subjects responding to both CD4 and CD8 epitopes (subjects 2, 3, and 5); blue circles: subjects responding to both CD4 spike and nonspike epitopes (subjects 12, 14, and 16). AIM+ CD4+ T cells showed a similar level of TEMRA, TEM, and TCM at follow-up visit compared with subacute MIS-C subjects (p > 0.05). AIM+ CD8+ T cells showed a slight increase in TEM (p > 0.05) and a similar level of TEMRA and TCM. (C) Percentage of DN T cells (left panel) and their responses to SARS-CoV-2 peptide megapools (right panels). Percentages of DN T cells were decreased in 5 subjects (2, 3, 5, 12, and 14) compared with subacute MIS-C subjects. One subject (3) showed DN T cell responses to SARS-CoV-2 CD4 and CD8 peptide megapools, and 2 subjects (14 and 16) showed DN T cell responses to SARS-CoV-2 CD4 spike and nonspike peptide megapools. (D) Percentage of CD4+ and CD8+ TcR Vβ21.3 (black bars, left panels). An amount of 2.0–3.9% of CD4+ T cells and 0.9–2.6% of CD8+ T cells were TCR Vβ21.3+ among the 6 subjects studied. TCR Vβ21.3+ CD4+ T cells in 1 subject (16) showed a minor response to a SARS-CoV-2 CD4 nonspike peptide megapool. Each symbol represents an individual subject. Comparisons of the percentage of AIM+ T cells between unstimulated control and peptide megapool-stimulated cell cultures were tested by the Wilcoxon signed-rank test. Comparisons of the memory phenotypes of AIM+ T cells between subacute and follow-up visit were tested by the Mann–Whitney U test.

T cell responses to peptide megapools derived from SARS-CoV-2 in MIS-C subjects healthy 6-14 months after the disease onset. Six MIS-C subjects (2, 3, 5, 12, 14, and 16) studied at their subacute phase were also studied 6–14 months later. Canonical CD4+ and CD8+, CD4− CD8− DN, and TCR Vβ21.3+ CD4+ and CD8+ T cell responses to SARS-CoV-2 peptide megapools were studied. The SI of AIM+ T cells from each individual subject was calculated to study the T cell responses. (A) CD4+ and CD8+ T cell responses to peptide megapools and their CCR6 expressions. Three subjects (2, 3, and 5) of the 6 subjects showed concurrent CD4+ and CD8+ T cell responses, and the other 3 follow-up MIS-C subjects (12, 14, and 16) showed only CD4+ T cell responses to SARS-CoV-2 (both CD4 spike (S) and nonspike (R) megapools). (B) Memory phenotypes of AIM+ CD4+ (left panels) and CD8+ (right panels) T cells. Red circles: subjects responding to both CD4 and CD8 epitopes (subjects 2, 3, and 5); blue circles: subjects responding to both CD4 spike and nonspike epitopes (subjects 12, 14, and 16). AIM+ CD4+ T cells showed a similar level of TEMRA, TEM, and TCM at follow-up visit compared with subacute MIS-C subjects (p > 0.05). AIM+ CD8+ T cells showed a slight increase in TEM (p > 0.05) and a similar level of TEMRA and TCM. (C) Percentage of DN T cells (left panel) and their responses to SARS-CoV-2 peptide megapools (right panels). Percentages of DN T cells were decreased in 5 subjects (2, 3, 5, 12, and 14) compared with subacute MIS-C subjects. One subject (3) showed DN T cell responses to SARS-CoV-2 CD4 and CD8 peptide megapools, and 2 subjects (14 and 16) showed DN T cell responses to SARS-CoV-2 CD4 spike and nonspike peptide megapools. (D) Percentage of CD4+ and CD8+ TcR Vβ21.3 (black bars, left panels). An amount of 2.0–3.9% of CD4+ T cells and 0.9–2.6% of CD8+ T cells were TCR Vβ21.3+ among the 6 subjects studied. TCR Vβ21.3+ CD4+ T cells in 1 subject (16) showed a minor response to a SARS-CoV-2 CD4 nonspike peptide megapool. Each symbol represents an individual subject. Comparisons of the percentage of AIM+ T cells between unstimulated control and peptide megapool-stimulated cell cultures were tested by the Wilcoxon signed-rank test. Comparisons of the memory phenotypes of AIM+ T cells between subacute and follow-up visit were tested by the Mann–Whitney U test.