CD8+ T cells specific for an immunodominant SARS-CoV-2 nucleocapsid epitope cross-react with selective seasonal coronaviruses

May 4, 2021Immunity

CD8+ T cells targeting a key SARS-CoV-2 protein may also recognize certain seasonal coronaviruses

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Abstract

The nucleocapsid (N) protein of SARS-CoV-2 may trigger a strong immune response in recovered COVID-19 patients and some unexposed individuals.

An immunodominant response was linked to a specific N-encoded epitope found in both COVID-19 recovered and unexposed donors.
This epitope is highly conserved among various circulating coronaviruses.
T cells showed cross-reactivity to seasonal coronaviruses OC43 and HKU-1, but not to 229E or NL63.
T cell receptor (TCR) analysis suggested that cross-reactivity involves specific TCRs, particularly with a preference for TRBV27.
These findings may indicate a potential for long-lasting protective immunity against similar coronaviruses.

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Efforts are being made worldwide to understand the immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for the coronavirus disease 2019 (COVID-19) pandemic, including the impact of T cell immunity and cross-recognition with seasonal coronaviruses. Screening of SARS-CoV-2 peptide pools revealed that the nucleocapsid (N) protein induced an immunodominant response in HLA-B7COVID-19-recovered individuals that was also detectable in unexposed donors. A single N-encoded epitope that was highly conserved across circulating coronaviruses drove this immunodominant response. In vitro peptide stimulation and crystal structure analyses revealed T cell-mediated cross-reactivity toward circulating OC43 and HKU-1 betacoronaviruses but not 229E or NL63 alphacoronaviruses because of different peptide conformations. T cell receptor (TCR) sequencing indicated that cross-reactivity was driven by private TCR repertoires with a bias for TRBV27 and a long CDR3β loop. Our findings demonstrate the basis of selective T cell cross-reactivity for an immunodominant SARS-CoV-2 epitope and its homologs from seasonal coronaviruses, suggesting long-lasting protective immunity. +

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Abstract

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