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SARS-CoV-2-specific CD8+ T-cell responses and TCR signatures in the context of a prominent HLA-A*24:02 allomorph.
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.
  • Rowntree LC; Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia.
  • Petersen J; Infection and Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia.
  • Juno JA; Australian Research Council Centre of Excellence for Advanced Molecular Imaging, Monash University, Clayton, VIC 3800, Australia.
  • Chaurasia P; Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia.
  • Wragg K; Infection and Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia.
  • Koutsakos M; Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia.
  • Hensen L; Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia.
  • Wheatley AK; Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia.
  • Kent SJ; Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia.
  • Rossjohn J; ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, University of Melbourne, Melbourne, VIC 3000, Australia.
  • Kedzierska K; Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia.
  • Nguyen TH; ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, University of Melbourne, Melbourne, VIC 3000, Australia.
Immunol Cell Biol ; 99(9): 990-1000, 2021 10.
Article in English | MEDLINE | ID: covidwho-1258941
Semantic information from SemMedBD (by NLM)
1. T cell mediated immunity PROCESS_OF Homo sapiens
Subject
T cell mediated immunity
Predicate
PROCESS_OF
Object
Homo sapiens
2. T cell mediated immunity ASSOCIATED_WITH COVID-19
Subject
T cell mediated immunity
Predicate
ASSOCIATED_WITH
Object
COVID-19
3. Epitope PART_OF C5203676
Subject
Epitope
Predicate
PART_OF
Object
C5203676
4. Epitopes PART_OF 2019 novel coronavirus
Subject
Epitopes
Predicate
PART_OF
Object
2019 novel coronavirus
5. COVID-19 PROCESS_OF Patients
Subject
COVID-19
Predicate
PROCESS_OF
Object
Patients
6. T cell mediated immunity PROCESS_OF Homo sapiens
Subject
T cell mediated immunity
Predicate
PROCESS_OF
Object
Homo sapiens
7. T cell mediated immunity ASSOCIATED_WITH COVID-19
Subject
T cell mediated immunity
Predicate
ASSOCIATED_WITH
Object
COVID-19
8. Epitopes, T-Lymphocyte PART_OF 2019 novel coronavirus
Subject
Epitopes, T-Lymphocyte
Predicate
PART_OF
Object
2019 novel coronavirus
9. Epitopes PART_OF 2019 novel coronavirus
Subject
Epitopes
Predicate
PART_OF
Object
2019 novel coronavirus
10. COVID-19 PROCESS_OF Patients
Subject
COVID-19
Predicate
PROCESS_OF
Object
Patients
ABSTRACT
In-depth understanding of human T-cell-mediated immunity in coronavirus disease 2019 (COVID-19) is needed if we are to optimize vaccine strategies and immunotherapies. Identification of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) T-cell epitopes and generation of peptide-human leukocyte antigen (peptide-HLA) tetramers facilitate 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*2402, 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+ IFNγ+ responses above background, S1208-1216 (QYIKWPWYI), S448-456 (NYNYLYRLF) and S193-201 (VFKNIDGYF), with S1208 generating immunodominant CD8+ IFNγ+ responses. Using peptide-HLA-I tetramers, we performed direct ex vivo tetramer enrichment for HLA-A*2402-restricted CD8+ T cells in COVID-19 patients and prepandemic controls. The precursor frequencies for HLA-A*2402-restricted epitopes were within the range previously observed for other SARS-CoV-2 epitopes for both COVID-19 patients and prepandemic individuals. Naïve A24/SARS-CoV-2-specific CD8+ T cells increased nearly 7.5-fold above the average precursor frequency during COVID-19, gaining effector and memory phenotypes. Ex vivo single-cell analyses of TCRαß repertoires found that the A24/S448 + CD8+ T-cell TCRαß repertoire was driven by a common TCRß chain motif, whereas the A24/S1208 + CD8+ TCRαß repertoire was diverse across COVID-19 patients. Our study provides an in depth characterization and important insights into SARS-CoV-2-specific CD8+ T-cell responses associated with a prominent HLA-A*2402 allomorph. This contributes to our knowledge on adaptive immune responses during primary COVID-19 and could be exploited in vaccine or immunotherapeutic approaches.
Subject(s)
Keywords

Full text: Available Collection: International databases Database: MEDLINE Main subject: Receptors, Antigen, T-Cell / CD8-Positive T-Lymphocytes / HLA-A24 Antigen / COVID-19 Type of study: Prognostic study Topics: Vaccines Limits: Humans Language: English Journal: Immunol Cell Biol Journal subject: Allergy and Immunology Year: 2021 Document Type: Article Affiliation country: Imcb.12482

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Receptors, Antigen, T-Cell / CD8-Positive T-Lymphocytes / HLA-A24 Antigen / COVID-19 Type of study: Prognostic study Topics: Vaccines Limits: Humans Language: English Journal: Immunol Cell Biol Journal subject: Allergy and Immunology Year: 2021 Document Type: Article Affiliation country: Imcb.12482