tetano
Editor, Senior Moderator
Cell Rep
. 2021 Dec 10;110167.
doi: 10.1016/j.celrep.2021.110167. Online ahead of print.
HLA-A [SUP]∗[/SUP] 02:01 restricted T cell receptors against the highly conserved SARS-CoV-2 polymerase cross-react with human coronaviruses
Pavlo A Nesterenko[SUP] 1 [/SUP], Jami McLaughlin[SUP] 2 [/SUP], Brandon L Tsai[SUP] 3 [/SUP], Giselle Burton Sojo[SUP] 2 [/SUP], Donghui Cheng[SUP] 4 [/SUP], Daniel Zhao[SUP] 3 [/SUP], Zhiyuan Mao[SUP] 5 [/SUP], Nathanael J Bangayan[SUP] 5 [/SUP], Matthew B Obusan[SUP] 2 [/SUP], Yapeng Su[SUP] 6 [/SUP], Rachel H Ng[SUP] 7 [/SUP], William Chour[SUP] 8 [/SUP], Jingyi Xie[SUP] 7 [/SUP], Yan-Ruide Li[SUP] 2 [/SUP], Derek Lee[SUP] 2 [/SUP], Miyako Noguchi[SUP] 2 [/SUP], Camille Carmona[SUP] 9 [/SUP], John W Phillips[SUP] 2 [/SUP], Jocelyn T Kim[SUP] 9 [/SUP], Lili Yang[SUP] 10 [/SUP], James R Heath[SUP] 11 [/SUP], Paul C Boutros[SUP] 12 [/SUP], Owen N Witte[SUP] 13 [/SUP]
Affiliations
Abstract
Cross-reactivity and direct killing of target cells remain underexplored for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-specific CD8[SUP]+[/SUP] T cells. Isolation of T cell receptors (TCRs) and overexpression in allogeneic cells allows for extensive T cell reactivity profiling. We identify SARS-CoV-2 RNA-dependent RNA polymerase (RdRp/NSP12) as highly conserved, likely due to its critical role in the virus life cycle. We perform single-cell TCRαβ sequencing in human leukocyte antigen (HLA)-A[SUP]∗[/SUP]02:01-restricted, RdRp-specific T cells from SARS-CoV-2-unexposed individuals. Human T cells expressing these TCRαβ constructs kill target cell lines engineered to express full-length RdRp. Three TCR constructs recognize homologous epitopes from common cold coronaviruses, indicating CD8[SUP]+[/SUP] T cells can recognize evolutionarily diverse coronaviruses. Analysis of individual TCR clones may help define vaccine epitopes that can induce long-term immunity against SARS-CoV-2 and other coronaviruses.
Keywords: CD8; COVID-19; SARS-CoV-2; T cells; TCR; antigen; cell therapy; immune response; single-cell; specific.
. 2021 Dec 10;110167.
doi: 10.1016/j.celrep.2021.110167. Online ahead of print.
HLA-A [SUP]∗[/SUP] 02:01 restricted T cell receptors against the highly conserved SARS-CoV-2 polymerase cross-react with human coronaviruses
Pavlo A Nesterenko[SUP] 1 [/SUP], Jami McLaughlin[SUP] 2 [/SUP], Brandon L Tsai[SUP] 3 [/SUP], Giselle Burton Sojo[SUP] 2 [/SUP], Donghui Cheng[SUP] 4 [/SUP], Daniel Zhao[SUP] 3 [/SUP], Zhiyuan Mao[SUP] 5 [/SUP], Nathanael J Bangayan[SUP] 5 [/SUP], Matthew B Obusan[SUP] 2 [/SUP], Yapeng Su[SUP] 6 [/SUP], Rachel H Ng[SUP] 7 [/SUP], William Chour[SUP] 8 [/SUP], Jingyi Xie[SUP] 7 [/SUP], Yan-Ruide Li[SUP] 2 [/SUP], Derek Lee[SUP] 2 [/SUP], Miyako Noguchi[SUP] 2 [/SUP], Camille Carmona[SUP] 9 [/SUP], John W Phillips[SUP] 2 [/SUP], Jocelyn T Kim[SUP] 9 [/SUP], Lili Yang[SUP] 10 [/SUP], James R Heath[SUP] 11 [/SUP], Paul C Boutros[SUP] 12 [/SUP], Owen N Witte[SUP] 13 [/SUP]
Affiliations
- PMID: 34919800
- DOI: 10.1016/j.celrep.2021.110167
Abstract
Cross-reactivity and direct killing of target cells remain underexplored for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-specific CD8[SUP]+[/SUP] T cells. Isolation of T cell receptors (TCRs) and overexpression in allogeneic cells allows for extensive T cell reactivity profiling. We identify SARS-CoV-2 RNA-dependent RNA polymerase (RdRp/NSP12) as highly conserved, likely due to its critical role in the virus life cycle. We perform single-cell TCRαβ sequencing in human leukocyte antigen (HLA)-A[SUP]∗[/SUP]02:01-restricted, RdRp-specific T cells from SARS-CoV-2-unexposed individuals. Human T cells expressing these TCRαβ constructs kill target cell lines engineered to express full-length RdRp. Three TCR constructs recognize homologous epitopes from common cold coronaviruses, indicating CD8[SUP]+[/SUP] T cells can recognize evolutionarily diverse coronaviruses. Analysis of individual TCR clones may help define vaccine epitopes that can induce long-term immunity against SARS-CoV-2 and other coronaviruses.
Keywords: CD8; COVID-19; SARS-CoV-2; T cells; TCR; antigen; cell therapy; immune response; single-cell; specific.