In this study, the Saeed lab discovered SARS-CoV-2 elements being identified by human T cells to initiate an immune attack against the virus. As a background, the human immune system has two arms: innate immunity and adaptive immunity. While innate immunity launches a quick, non-specific fight against the virus, adaptive immunity is slow and utilizes specific viral components to get activated and unleash severe attack on the virus. A distinctive feature of adaptive immunity is that it “remembers” the viral identity, and if encountered by the same virus in the future, sets in motion a quick and intense campaign to overpower the virus. The adaptive immunity can be further divided into two subgroups: B cell immunity (a.k.a. humoral immunity) and T cell immunity (a.k.a. cellular immunity). While B cell immunity acts by generating antibodies against the virus, T cell immunity employs specialized cells to destroy the virus-infected cells.
Although a number of studies have reported SARS-CoV-2 elements being recognized by human B cells to produce antibodies, there remained a paucity of knowledge regarding viral components being identified by human T cells, and this is despite the fact that the role of T cells in SARS-CoV-2 clearance has been increasingly recognized. To fill this knowledge gap, the Saeed lab collaborated with a research group at the Broad Institute of MIT and Harvard and performed mass spectrometry-based analysis of viral peptides (protein fragments) that have the ability to activate T cells. This led to the discovery of 37 peptides. Strikingly, eight of these peptides originated from the hidden, non-canonical SARS-CoV-2 proteins that are often overlooked by the scientists.
The team then performed a series of experiments in human and mice to test if the identified viral peptides were capable of activating T cells. Most of them indeed were. To scientists’ surprise, some peptides derived from the hidden viral proteins provoked the strongest immune response, highlighting an unexpected yet critical role of these proteins in virus biology. These findings will change the way scientists study the human immune responses to SARS-CoV-2 and will also inform the development of next-generation vaccines. Incorporation of viral components capable of invoking strong T cell responses is expected to produce a vaccine that is more effective and broadly protective against newly emerging SARS-CoV-2 variants.
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