Clonal analysis of the immunodominance and cross-reactivity of the CD4 T cell response to SARS-CoV-2

Probe the immunity of CD4 T lymphocytes to SARS-CoV-2

Better understanding of CD4+ T cell responses to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) are crucial for the design of effective next-generation vaccines. Low et al. defined and estimated CD4+ Directory of T lymphocytes in convalescent COVID-19 patients. After sorting various CD4s+ Subsets of T cells, they generated numerous T cell clones that reacted to the SARS-CoV-2 spike protein. A large number of T cell clones from almost all individuals recognized a small conserved immunodominant region in the spike protein receptor binding (RBD) domain. The researchers isolated T cell clones that broadly reacted to the spike protein of other coronaviruses, providing evidence of the recall of preexisting cross-reacting memory T cells after infection with SARS-CoV-2.

Science, abg8985, this issue p. 1336


Identification of CD4+ T cell epitopes play a critical role in the design of subunit vaccines for broad protection against coronaviruses. Here, we demonstrate in individuals recovered by COVID-19 a robust CD4+ T cell response to naturally processed Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) spike protein (S) and nucleoprotein (N), including effector, helper and memory T cells. By characterizing 2943 S-reactive T cell clones from 34 individuals, we found that the receptor binding domain (RBD) is highly immunogenic and that 33% of RBD-reactive clones and 94% of individuals recognized a conserved immunodominant region. S346-S365 comprising epitopes restricted to human leukocyte antigen DR (HLA-DR) and HLA-DP. Using pre- and post-COVID-19 samples and endemic coronavirus S proteins, we identified cross-reacting T cells targeting multiple S-protein sites. Identified immunodominant and cross-reacting epitopes can shed light on vaccination strategies to counter emerging variants of SARS-CoV-2.

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About Mark A. Tomlin

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