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

Article Article scientifique Article HLA variants and TCR diversity against SARS-CoV-2 in the pre-COVID-19 era eng 2023-07-18 2023-12 author Buhler Stéphane 0000-0001-6675-5287 Transplantation Immunology Unit and National Reference Laboratory for Histocompatibility, Department of Diagnostic, Geneva University Hospitals, Geneva, Switzerland. 502714 Département de médecine (DEMED) author Calderin Sollet Zuleika Transplantation Immunology Unit and National Reference Laboratory for Histocompatibility, Department of Diagnostic, Geneva University Hospitals, Geneva, Switzerland. 719944 Département de chirurgie (CHIRU) author Studer Florence Transplantation Immunology Unit and National Reference Laboratory for Histocompatibility, Department of Diagnostic, Geneva University Hospitals, Geneva, Switzerland. 124912 author Schaefer Antonia Marie Transplantation Immunology Unit and National Reference Laboratory for Histocompatibility, Department of Diagnostic, Geneva University Hospitals, Geneva, Switzerland. 952870 author Ansari Djaberi Marc Georges CANSEARCH Research Platform for Pediatric Oncology and Hematology, Faculty of Medicine, Department of Pediatrics, Gynecology and Obstetrics, University of Geneva, Geneva, Switzerland.,Division of Pediatric Oncology and Hematology, Department of Women, Child and Adolescent, University Geneva Hospitals, Geneva, Switzerland. 61572 Département de Pédiatrie, Gynécologie et Obstétrique (PETRI) author Ferrari-Lacraz Sylvie Transplantation Immunology Unit and National Reference Laboratory for Histocompatibility, Department of Diagnostic, Geneva University Hospitals, Geneva, Switzerland. 36049 Département de médecine (DEMED) author Villard Jean 0000-0003-2667-7506 Transplantation Immunology Unit and National Reference Laboratory for Histocompatibility, Department of Diagnostic, Geneva University Hospitals, Geneva, Switzerland. 29595 Département de médecine (DEMED) 720-730 10.1111/tan.15158 37461808 2059-2302 https://onlinelibrary.wiley.com/doi/10.1111/tan.15158 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. HLA SARS-CoV-2 TCR Diversity Heterologous immunity Immune reconstitution Humans COVID-19 Alleles Receptors, Antigen, T-Cell / genetics Antibodies Peptides Dewey 616 Dewey 618 Swiss National Science Foundation New insights in the immunogenetics of haematopoietic stem cell transplantation 173237 CH Projects 58 Département de pédiatrie, gynécologie et obstétrique 223 56 Département de médecine 221 false 564 Oncologie et hématologie pédiatriques 907 298 Immunologie de transplantation, immunogénétique et thérapie cellulaire 561 https://yareta.unige.ch/archives/d3b7ff0a-1cce-4812-a30a-86d5b5437e65 HLA 102 6 0cb16010-4a91-49f3-946b-2fdc7161cb65 Article (Published version) Public HLA.pdf 1985885 application/pdf CC BY-NC-ND-4.0 830f3685d178da31e6ae0d7f9f8d3939669fa2c1d4595c901c498e7b78f4a8cb fd17a2d2-fe21-4bed-ac88-f0509302372b Supplemental data Public tan15158-sup-0001-supplementary_inf.pdf 164537 application/pdf 51fcbbf9f4c9cf881069561535ebe06a1dcd6f01e6d74683fdddeaf6ec2c34d6 openAccess Faculté de médecine / Section de médecine clinique / Département de pédiatrie, gynécologie et obstétrique Faculté de médecine / Section de médecine clinique / Département de médecine

Title	Published in	Year	Views	Downloads

HLA variants and TCR diversity against SARS-CoV-2 in the pre-COVID-19 era	HLA	2023	108	95
CD8+ T-Cell Repertoire in Human Leukocyte Antigen Class I-Mismatched Alloreactive Immune Response	Frontiers in Immunology	2020	244	226

Archive ouverte UNIGE

Studer, Florence