Selected article for: "cell receptor and effector memory"

Author: Rowntree, Louise C; Petersen, Jan; Juno, Jennifer A; Chaurasia, Priyanka; Wragg, Kathleen; Koutsakos, Marios; Hensen, Luca; Wheatley, Adam K; Kent, Stephen J; Rossjohn, Jamie; Kedzierska, Katherine; Nguyen, Thi HO
Title: SARS‐CoV‐2‐specific CD8(+) T‐cell responses and TCR signatures in the context of a prominent HLA‐A*24:02 allomorph
  • Cord-id: coyz6wm5
  • Document date: 2021_6_4
  • ID: coyz6wm5
    Snippet: In‐depth understanding of human T cell‐mediated immunity in COVID‐19 is needed if we are to optimize vaccine strategies and immunotherapies. Identification of SARS‐CoV‐2 T cell epitopes and generation of peptide‐HLA tetramers facilitates direct ex vivo analyses of SARS‐CoV‐2‐specific T cells and their T cell receptor (TCR) repertoires. We utilized a combination of peptide prediction and in vitro peptide stimulation to validate novel SARS‐CoV‐2 epitopes restricted by HLA‐A
    Document: In‐depth understanding of human T cell‐mediated immunity in COVID‐19 is needed if we are to optimize vaccine strategies and immunotherapies. Identification of SARS‐CoV‐2 T cell epitopes and generation of peptide‐HLA tetramers facilitates direct ex vivo analyses of SARS‐CoV‐2‐specific T cells and their T cell receptor (TCR) repertoires. We utilized a combination of peptide prediction and in vitro peptide stimulation to validate novel SARS‐CoV‐2 epitopes restricted by HLA‐A*24:02, one of the most prominent HLA class I alleles, especially in Indigenous and Asian populations. Of the peptides screened, three spike‐derived peptides generated CD8(+)IFN‐γ(+) responses above background, S(1208‐1216) (QYIKWPWYI), S(448‐456) (NYNYLYRLF) and S(193‐201) (VFKNIDGYF), with S(1208) generating immunodominant CD8(+)IFN‐γ(+) responses. Using peptide‐HLA‐I tetramers, we performed direct ex vivo tetramer enrichment for HLA‐A*24:02‐restricted CD8(+) T cells in COVID‐19 patients and pre‐pandemic controls. The precursor frequencies for HLA‐A*24:02‐restricted epitopes were within the range previously observed for other SARS‐CoV‐2 epitopes for both COVID‐19 patients and pre‐pandemic individuals. Naïve A24/SARS‐CoV‐2‐specific CD8(+) T cells increased ~7.5‐fold above the average precursor frequency during COVID‐19, gaining effector and memory phenotypes. Ex vivo single‐cell analyses of TCRαβ repertoires found that the A24/S(448) (+)CD8(+) T cell TCRαβ repertoire was driven by a common TCRβ chain motif, while the A24/S(1208) (+)CD8(+) TCRαβ repertoire was diverse across COVID‐19 patients. Our study provides an in depth characterisation and important insights into SARS‐CoV‐2‐specific CD8(+) T cell responses associated with a prominent HLA‐A*24:02 allomorph. This contributes to our knowledge on adaptive immune responses during primary COVID‐19 and could be exploited in vaccine or immunotherapeutic approaches.

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