HLA variants and TCR diversity against SARS-CoV-2 in the pre-COVID-19 era.
HLA
SARS-CoV-2
TCR
diversity
heterologous immunity
immune reconstitution
Journal
HLA
ISSN: 2059-2310
Titre abrégé: HLA
Pays: England
ID NLM: 101675570
Informations de publication
Date de publication:
12 2023
12 2023
Historique:
revised:
03
07
2023
received:
08
12
2022
accepted:
06
07
2023
medline:
13
11
2023
pubmed:
18
7
2023
entrez:
18
7
2023
Statut:
ppublish
Résumé
HLA antigen presentation and T-cell mediated immunity are critical to control acute viral infection such as COVID-19 caused by SARS-CoV-2. Recent data suggest that both the depth of peptide presentation and the breadth of the T-cell repertoire are associated with disease outcome. It has also been shown that unexposed subjects can develop strong T-cell responses against SARS-CoV-2 due to heterologous immunity. In this study, we explored the anti-SARS-CoV-2 T-cell repertoire by analyzing previously published T-cell receptor (TCR) CDR3β immunosequencing data in a cohort of 116 healthy donors and in the context of immune reconstitution after allogeneic hematopoietic stem cell transplantation in 116 recipients collected during the pre-COVID-19 era. For this, 143,310 publicly available SARS-CoV-2 specific T-cell sequences were investigated among the 3.5 million clonotypes in the cohort. We also performed HLA class I peptide binding predictions using the reference proteome of the virus and high resolution genotyping data in these patients. We could demonstrate that individuals are fully equipped at the genetic level to recognize SARS-CoV-2. This is evidenced by the 5% median cumulative frequency of clonotypes having their sequence matched to a SARS-CoV-2 specific T-cell. In addition, any combination of HLA class I variants in this cohort is associated with a broad capacity of presenting hundreds of SARS-CoV-2 derived peptides. These results could be explained by heterologous immunity and random somatic TCR recombination. We speculate that these observations could explain the efficacy of the specific immune response against SARS-CoV-2 in individuals without risk factors of immunodeficiency and infected prior to vaccination.
Substances chimiques
Receptors, Antigen, T-Cell
0
Antibodies
0
Peptides
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
720-730Informations de copyright
© 2023 The Authors. HLA: Immune Response Genetics published by John Wiley & Sons Ltd.
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