tetano
Editor, Senior Moderator
Nat Immunol
. 2022 Apr 5.
doi: 10.1038/s41590-022-01184-4. Online ahead of print.
SARS-CoV-2 antigen exposure history shapes phenotypes and specificity of memory CD8 [SUP]+[/SUP] T cells
Anastasia A Minervina[SUP] #[/SUP][SUP] 1 [/SUP], Mikhail V Pogorelyy[SUP] #[/SUP][SUP] 1 [/SUP], Allison M Kirk[SUP] 1 [/SUP], Jeremy Chase Crawford[SUP] 1 [/SUP], E Kaitlynn Allen[SUP] 1 [/SUP], Ching-Heng Chou[SUP] 1 [/SUP], Robert C Mettelman[SUP] 1 [/SUP], Kim J Allison[SUP] 2 [/SUP], Chun-Yang Lin[SUP] 1 [/SUP], David C Brice[SUP] 1 [/SUP], Xun Zhu[SUP] 3 [/SUP], Kasi Vegesana[SUP] 4 [/SUP], Gang Wu[SUP] 3 [/SUP], Sanchit Trivedi[SUP] 5 [/SUP], Pratibha Kottapalli[SUP] 5 [/SUP], Daniel Darnell[SUP] 5 [/SUP], Suzanne McNeely[SUP] 5 [/SUP], Scott R Olsen[SUP] 5 [/SUP], Stacey Schultz-Cherry[SUP] 2 [/SUP], Jeremie H Estepp[SUP] 6 [/SUP], SJTRC Study Team; Maureen A McGargill[SUP] 1 [/SUP], Joshua Wolf[SUP] 7 [/SUP], Paul G Thomas[SUP] 8 [/SUP]
Collaborators, Affiliations
Abstract
Although mRNA vaccine efficacy against severe coronavirus disease 2019 remains high, variant emergence has prompted booster immunizations. However, the effects of repeated exposures to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigens on memory T cells are poorly understood. Here, we utilize major histocompatibility complex multimers with single-cell RNA sequencing to profile SARS-CoV-2-responsive T cells ex vivo from humans with one, two or three antigen exposures, including vaccination, primary infection and breakthrough infection. Exposure order determined the distribution between spike-specific and non-spike-specific responses, with vaccination after infection leading to expansion of spike-specific T cells and differentiation to CCR7[SUP]-[/SUP]CD45RA[SUP]+[/SUP] effectors. In contrast, individuals after breakthrough infection mount vigorous non-spike-specific responses. Analysis of over 4,000 epitope-specific T cell antigen receptor (TCR) sequences demonstrates that all exposures elicit diverse repertoires characterized by shared TCR motifs, confirmed by monoclonal TCR characterization, with no evidence for repertoire narrowing from repeated exposure. Our findings suggest that breakthrough infections diversify the T cell memory repertoire and current vaccination protocols continue to expand and differentiate spike-specific memory.
. 2022 Apr 5.
doi: 10.1038/s41590-022-01184-4. Online ahead of print.
SARS-CoV-2 antigen exposure history shapes phenotypes and specificity of memory CD8 [SUP]+[/SUP] T cells
Anastasia A Minervina[SUP] #[/SUP][SUP] 1 [/SUP], Mikhail V Pogorelyy[SUP] #[/SUP][SUP] 1 [/SUP], Allison M Kirk[SUP] 1 [/SUP], Jeremy Chase Crawford[SUP] 1 [/SUP], E Kaitlynn Allen[SUP] 1 [/SUP], Ching-Heng Chou[SUP] 1 [/SUP], Robert C Mettelman[SUP] 1 [/SUP], Kim J Allison[SUP] 2 [/SUP], Chun-Yang Lin[SUP] 1 [/SUP], David C Brice[SUP] 1 [/SUP], Xun Zhu[SUP] 3 [/SUP], Kasi Vegesana[SUP] 4 [/SUP], Gang Wu[SUP] 3 [/SUP], Sanchit Trivedi[SUP] 5 [/SUP], Pratibha Kottapalli[SUP] 5 [/SUP], Daniel Darnell[SUP] 5 [/SUP], Suzanne McNeely[SUP] 5 [/SUP], Scott R Olsen[SUP] 5 [/SUP], Stacey Schultz-Cherry[SUP] 2 [/SUP], Jeremie H Estepp[SUP] 6 [/SUP], SJTRC Study Team; Maureen A McGargill[SUP] 1 [/SUP], Joshua Wolf[SUP] 7 [/SUP], Paul G Thomas[SUP] 8 [/SUP]
Collaborators, Affiliations
- PMID: 35383307
- DOI: 10.1038/s41590-022-01184-4
Abstract
Although mRNA vaccine efficacy against severe coronavirus disease 2019 remains high, variant emergence has prompted booster immunizations. However, the effects of repeated exposures to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigens on memory T cells are poorly understood. Here, we utilize major histocompatibility complex multimers with single-cell RNA sequencing to profile SARS-CoV-2-responsive T cells ex vivo from humans with one, two or three antigen exposures, including vaccination, primary infection and breakthrough infection. Exposure order determined the distribution between spike-specific and non-spike-specific responses, with vaccination after infection leading to expansion of spike-specific T cells and differentiation to CCR7[SUP]-[/SUP]CD45RA[SUP]+[/SUP] effectors. In contrast, individuals after breakthrough infection mount vigorous non-spike-specific responses. Analysis of over 4,000 epitope-specific T cell antigen receptor (TCR) sequences demonstrates that all exposures elicit diverse repertoires characterized by shared TCR motifs, confirmed by monoclonal TCR characterization, with no evidence for repertoire narrowing from repeated exposure. Our findings suggest that breakthrough infections diversify the T cell memory repertoire and current vaccination protocols continue to expand and differentiate spike-specific memory.