T cells are among the immune system's most powerful weapons, but their importance for battling SARS-CoV-2, the virus that causes COVID-19, has been unclear. Now, two studies show infected people harbor T cells that target the virus—and may help them recover. Both studies also found that some people never infected with SARS-CoV-2 have these cellular defenses, most likely because they were previously infected with other coronaviruses that cause the common cold.

“This is encouraging data,” says virologist Angela Rasmussen of Columbia University, who wasn't involved in the work. Although the studies don't clarify whether people who clear a SARS-CoV-2 infection can ward off the virus in the future, both identified strong T cell responses to it, which “bodes well for the development of long-term protective immunity,” Rasmussen says. The findings could also help researchers create better vaccines.

The more than 100 COVID-19 vaccines in development mainly focus on triggering a different immune response: antibodies. Researchers know our B cells make antibodies against SARS-CoV-2, which vaccine developers hope can latch onto the virus and prevent it from entering cells. But T cells can also help thwart infections. Helper T cells spur B cells and other immune defenders into action, whereas killer T cells target and destroy infected cells. The severity of disease can depend on the strength of these T cell responses.

To determine whether the new coronavirus provokes T cells, a team led by Shane Crotty and Alessandro Sette, immunologists at the La Jolla Institute for Immunology, used bioinformatics tools to predict which segments of the virus' proteins should stimulate T cells most effectively. They then exposed immune cells from 10 patients who had recovered from mild cases of COVID-19 to these viral snippets...

...The results have other significant implications for vaccine design, says molecular virologist Rachel Graham of the University of North Carolina, Chapel Hill. Most vaccines under development aim to elicit an immune response against the spike protein, but the La Jolla group's study determined that T cells reacted to several viral proteins, suggesting vaccines that incite an immune response to these proteins as well could be more effective. “It is important to not just concentrate on one protein,” Graham says...

Grifoni, A., Weiskopf, D., Ramirez, S.I., Mateus, J., Dan, J.M., Moderbacher,C.R., Rawlings, S.A., Sutherland, A., Premkumar, L., Jadi, R.S., Marrama, D., de Silva, A.M., Frazier, A.,Carlin, A., Greenbaum, J.A., Peters, B., Krammer, F., Smith, D.M., Crotty, S., Sette, A., Targets of T cellresponses to SARS-CoV-2 coronavirus in humans with COVID-19 disease and unexposed individuals,Cell (2020), doi: https://doi.org/10.1016/j.cell.2020.05.015.

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