Cross-reactivity of SARS-CoV-2– and influenza A–specific T cells in individuals exposed to SARS-CoV-2
Worarat Chaisawangwong, … , Avi Z. Rosenberg, Jonathan P. Schneck
Worarat Chaisawangwong, … , Avi Z. Rosenberg, Jonathan P. Schneck
Published September 22, 2022
Citation Information: JCI Insight. 2022;7(18):e158308. https://doi.org/10.1172/jci.insight.158308.
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Research Article COVID-19 Immunology

Cross-reactivity of SARS-CoV-2– and influenza A–specific T cells in individuals exposed to SARS-CoV-2

Abstract

Cross-reactive immunity between SARS-CoV-2 and other related coronaviruses has been well-documented, and it may play a role in preventing severe COVID-19. Epidemiological studies early in the pandemic showed a geographical association between high influenza vaccination rates and lower incidence of SARS-CoV-2 infection. We, therefore, analyzed whether exposure to influenza A virus (IAV) antigens could influence the T cell repertoire in response to SARS-CoV-2, indicating a heterologous immune response between these 2 unrelated viruses. Using artificial antigen-presenting cells (aAPCs) combined with real-time reverse-transcription PCR (RT-qPCR), we developed a sensitive assay to quickly screen for antigen-specific T cell responses and detected a significant correlation between responses to SARS-CoV-2 epitopes and IAV dominant epitope (M158–66). Further analysis showed that some COVID-19 convalescent donors exhibited both T cell receptor (TCR) specificity and functional cytokine responses to multiple SARS-CoV-2 epitopes and M158–66. Utilizing an aAPC-based stimulation/expansion assay, we detected cross-reactive T cells with specificity to SARS-CoV-2 and IAV. In addition, TCR sequencing of the cross-reactive and IAV-specific T cells revealed similarities between the TCR repertoires of the two populations. These results indicate that heterologous immunity shaped by our exposure to other unrelated endemic viruses may affect our immune response to novel viruses such as SARS-CoV-2.

Authors

Worarat Chaisawangwong, Hanzhi Wang, Theodore Kouo, Sebastian F. Salathe, Ariel Isser, Joan Glick Bieler, Maya L. Zhang, Natalie K. Livingston, Shuyi Li, Joseph J. Horowitz, Ron E. Samet, Israel Zyskind, Avi Z. Rosenberg, Jonathan P. Schneck

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Figure 1

Antigen-specific T cell responses using a rapid aAPC-based assay.

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Antigen-specific T cell responses using a rapid aAPC-based assay. (A) Sc...
(A) Schematic view of the experimental workflow for determining IFNG mRNA fold change using aAPC and 1-step RT-qPCR. (B) Schematic illustration of adaptive aAPC process. Unloaded MHC dimer and αCD28 are first conjugated to magnetic particles. Peptides of interest are then passively loaded onto the empty MHC by coincubation to generate peptide-specific aAPC. (C) IFNG fold change after stimulation for 3 hours with either aAPC or soluble peptide in matched samples. Significance was determined by 2-tailed Wilcoxon matched-pairs signed rank test (n = 7). (D) Comparison of median IFNG fold change above that of unstimulated samples in convalescent (n = 24) versus uninfected individuals (n = 11). Median fold change above that of matched unstimulated samples in IFNG mRNA after stimulation with pooled 6 SARS-CV2 peptide–aAPCs (shown in Supplemental Table 1). Significance was determined by 2-tailed Mann-Whitney U test, with threshold of P ≤ 0.05 (E) Comparison of median IFNG fold change above that of unstimulated samples in convalescent (n = 9) versus uninfected individuals (n = 3) followed longitudinally. Median fold change that of above matched unstimulated samples in IFNG mRNA after stimulation with batched peptide-aAPC. Significance was determined by 2-tailed Mann-Whitney U test, with threshold of P ≤ 0.05.