Cross-reactivity of SARS-CoV-2- and influenza A-specific T cells in individuals exposed to SARS-CoV-2.
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
Author Information
Worarat Chaisawangwong: Department of Pathology, School of Medicine.
Hanzhi Wang: Department of Biomedical Engineering, Whiting School of Engineering.
Theodore Kouo: Department of Pediatrics, Division of Emergency Medicine.
Sebastian F Salathe: Department of Pathology, School of Medicine.
Ariel Isser: Department of Biomedical Engineering, School of Medicine, and.
Joan Glick Bieler: Department of Pathology, School of Medicine.
Maya L Zhang: Department of Biomedical Engineering, Whiting School of Engineering.
Natalie K Livingston: Department of Biomedical Engineering, School of Medicine, and.
Shuyi Li: Department of Pathology, School of Medicine.
Joseph J Horowitz: ExpressCare Urgent Care, Bel Air, Maryland, USA.
Ron E Samet: Department of Anesthesiology, University of Maryland School of Medicine, Baltimore, Maryland, USA.
Israel Zyskind: Department of Pediatrics, NYU Langone Medical Center, New York, New York, USA; Maimonides Medical Center, New York, New York, USA.
Avi Z Rosenberg: Department of Pathology, School of Medicine.
Jonathan P Schneck: Department of Pathology, School of Medicine.
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.
