Scientific article
OA Policy
English

HLA variants and TCR diversity against SARS-CoV-2 in the pre-COVID-19 era

Published inHLA, vol. 102, no. 6, p. 720-730
Publication date2023-12
First online date2023-07-18
Abstract

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.

Keywords
  • HLA
  • SARS-CoV-2
  • TCR
  • Diversity
  • Heterologous immunity
  • Immune reconstitution
  • Humans
  • COVID-19
  • Alleles
  • Receptors, Antigen, T-Cell / genetics
  • Antibodies
  • Peptides
Citation (ISO format)
BUHLER, Stéphane et al. HLA variants and TCR diversity against SARS-CoV-2 in the pre-COVID-19 era. In: HLA, 2023, vol. 102, n° 6, p. 720–730. doi: 10.1111/tan.15158
Main files (1)
Article (Published version)
Secondary files (1)
Supplemental data
accessLevelPublic
Identifiers
Journal ISSN2059-2302
115views
114downloads

Technical informations

Creation04/11/2024 10:28:46
First validation04/12/2024 09:13:52
Update13/10/2025 12:20:46
Status update04/12/2024 09:13:52
Last indexation29/10/2026 12:22:09
All rights reserved by Archive ouverte UNIGE and the University of GenevaunigeBlack
Open AIRE Indexed & Validated