Count on us: T cells in SARS-CoV-2 infection and vaccination

Abstract

Robust T cell responses have been associated with milder outcomes in many infections. T cells also establish long-term memory pools and, as they are predominantly directed toward epitopes encompassing conserved peptides, can respond to SARS-CoV-2 variants, including Omicron. Here, we discuss epitope-specific CD8⁺ and CD4⁺ T cell responses toward SARS-CoV-2 infection and vaccination, their subsequent persistence into long-term memory, and ongoing work to determine their role in limiting disease severity.

Figure 1

Defining the features of protective T cell immunity (A) Distinct antigenic histories generate differing levels of T cell memory targeting various viral targets. To date all approved vaccines have relied solely on Spike antigens, generating only Spike-specific memory. In most convalescent individuals, Spike responses are a significant minority of the repertoire but are further expanded by vaccine boosters. (B) Immunodominance hierarchies have been defined for CD4⁺ and CD8⁺ T cell responses with some epitopes being targeted by up to 10% of CD4⁺ or CD8⁺ compartment. The consequences of differential epitope targeting remain to be defined. (C) The spectrum of T cell specificity and magnitude generated in convalescent and vaccinated individuals may be driving variation in clinical outcomes, but rigorous correlates of protection of the T cell response have yet to be reported. Created with BioRender.com.