Antibodies—Y-shaped proteins that recognize and neutralize pathogens—have so far dominated discussions about how to beat COVID-19; however, there are signs that the antibody response may be short-lived. Meanwhile, increasing evidence is showing that a second branch of the immune system that uses T cells, a type of white blood cell that ‘remembers’ a pathogen for quick destruction, deserves a closer look.
“T cells, and not only antibodies, are an essential part of antiviral immunity,” noted Antonio Bertoletti, a Professor at Duke-NUS Medical School’s Emerging Infectious Diseases Program and an Adjunct Principal Investigator at A*STAR’s Singapore Immunology Network (SIgN). “This concept has been present in the scientific community for over 50 years, but so far has been largely ignored in discussions related to COVID-19 immunity.”
In a study published in Nature, Bertoletti and his collaborators in Singapore sought to introduce a more ‘balanced’ view of the conversation about COVID-19 immunity. They did so by characterizing the SARS-CoV-2-specific T cell response in patients who have recovered from the severe acute respiratory syndrome (SARS) and COVID-19, as compared to uninfected healthy individuals.
Because SARS-CoV-2 is made up of several different proteins, the researchers analyzed whether the patients’ T cells recognize nucleocapsid (N) protein, an abundant structural protein, and NSP7 and NSP13, two non-structural proteins.
“It is important to understand whether it is the structural proteins or the non-structural proteins (proteins necessary for replication but not structure) of the virus that can elicit a T cell response,” explained Yee-Joo Tan, a Principal Investigator at A*STAR’s Institute of Molecular and Cell Biology (IMCB) who initiated this study with the Duke-NUS team.
Of the 36 COVID-19-recovered patients tested, all produced T cell responses against the N protein and less so against the non-structural proteins, as did all 23 SARS-recovered patients tested 17 years after infection. This result suggests long-lasting cross-reactivity between the T cells that recognize SARS-CoV-1 and SARS-CoV-2.
Surprisingly, half of the 37 uninfected individuals also showed a T cell response against SARS-CoV-2. Unlike SARS and COVID-19-recovered patients, who showed a dominant T cell response to the N protein, T cells from uninfected individuals recognized both structural and non-structural proteins. These cross-reactive T cells have likely been induced by contact or infection with other coronaviruses.
“There is this idea of the total absence of immunity against coronaviruses in the general population, which is clearly incorrect,” said Bertoletti. “Other coronaviruses have always been circulating in humans.”
The next step is to determine whether memory T cells can protect against or change the pathogenesis of COVID-19. This study will require a large sample of exposed uninfected individuals, Bertoletti said.
The A*STAR-affiliated researchers contributing to this research are from the Singapore Immunology Network (SIgN) and the Institute of Molecular and Cell Biology (IMCB).
