Perturbations of the T-cell receptor repertoire in response to SARS-CoV-2 in immunocompetent and immunocompromised individuals

Ottavia M Delmonte; Cihan Oguz; Kerry Dobbs; Katherine Myint-Hpu; Boaz Palterer; Michael S Abers; Deborah Draper; Meng Truong; Ian M Kaplan; Rachel M Gittelman; Yu Zhang; Lindsey B Rosen; Andrew L Snow; Clifton L Dalgard; Peter D Burbelo; Luisa Imberti; Alessandra Sottini; Eugenia Quiros-Roldan; Francesco Castelli; Camillo Rossi; Duilio Brugnoni; Andrea Biondi; Laura Rachele Bettini; Mariella D'Angio; Paolo Bonfanti; Megan V Anderson; Annalisa Saracino; Maria Chironna; Mariantonietta Di Stefano; Jose Ramon Fiore; Teresa Santantonio; Riccardo Castagnoli; Gian Luigi Marseglia; Mary Magliocco; Marita Bosticardo; Francesca Pala; Elana Shaw; Helen Matthews; Sarah E Weber; Sandhya Xirasagar; Jason Barnett; Andrew J Oler; Dimana Dimitrova; Jenna R E Bergerson; David H McDermott; V Koneti Rao; Philip M Murphy; Steven M Holland; Andrea Lisco; Helen C Su; Michail S Lionakis; Jeffrey I Cohen; Alexandra F Freeman; Thomas M Snyder; Justin Lack; Luigi D Notarangelo

doi:10.1016/j.jaci.2023.12.011

Perturbations of the T-cell receptor repertoire in response to SARS-CoV-2 in immunocompetent and immunocompromised individuals

J Allergy Clin Immunol. 2023 Dec 27:S0091-6749(23)02544-7. doi: 10.1016/j.jaci.2023.12.011. Online ahead of print.

Authors

Ottavia M Delmonte¹, Cihan Oguz², Kerry Dobbs³, Katherine Myint-Hpu³, Boaz Palterer³, Michael S Abers³, Deborah Draper³, Meng Truong³, Ian M Kaplan⁴, Rachel M Gittelman⁴, Yu Zhang³, Lindsey B Rosen³, Andrew L Snow⁵, Clifton L Dalgard⁶, Peter D Burbelo⁷, Luisa Imberti⁸, Alessandra Sottini⁸, Eugenia Quiros-Roldan⁹, Francesco Castelli⁹, Camillo Rossi¹⁰, Duilio Brugnoni¹¹, Andrea Biondi¹², Laura Rachele Bettini¹², Mariella D'Angio¹², Paolo Bonfanti¹³, Megan V Anderson¹⁴, Annalisa Saracino¹⁵, Maria Chironna¹⁶, Mariantonietta Di Stefano¹⁷, Jose Ramon Fiore¹⁷, Teresa Santantonio¹⁷, Riccardo Castagnoli¹⁸, Gian Luigi Marseglia¹⁸, Mary Magliocco¹⁹, Marita Bosticardo³, Francesca Pala³, Elana Shaw³, Helen Matthews¹⁹, Sarah E Weber¹⁹, Sandhya Xirasagar²⁰, Jason Barnett²⁰, Andrew J Oler²⁰, Dimana Dimitrova²¹, Jenna R E Bergerson³, David H McDermott²², V Koneti Rao³, Philip M Murphy²², Steven M Holland³, Andrea Lisco¹⁴, Helen C Su³, Michail S Lionakis³, Jeffrey I Cohen²³, Alexandra F Freeman³, Thomas M Snyder⁴, Justin Lack², Luigi D Notarangelo²⁴

Affiliations

¹ Laboratory of Clinical Immunology and Microbiology National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Md. Electronic address: ottavia.delmonte@nih.gov.
² Integrated Data Sciences Section, Research Technology Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Md.
³ Laboratory of Clinical Immunology and Microbiology National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Md.
⁴ Adaptive Biotechnologies, Seattle, Wash.
⁵ Laboratory of Clinical Immunology and Microbiology National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Md; Department of Pharmacology & Molecular Therapeutics, Uniformed Services University of the Health Sciences, Bethesda, Md.
⁶ Department of Anatomy, Physiology & Genetics, Uniformed Services University of the Health Sciences, Bethesda, Md; The American Genome Center, Uniformed Services University of the Health Sciences, Bethesda, Md.
⁷ Adeno-Associated Virus Biology Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Md.
⁸ Section of Microbiology, University of Brescia, ASST Spedali Civili, Brescia, Italy.
⁹ Department of Infectious and Tropical Diseases, University of Brescia, ASST Spedali Civili, Brescia, Italy.
¹⁰ Direzione Sanitaria, ASST Spedali Civili, Brescia, Italy.
¹¹ Laboratorio Analisi Chimico-Cliniche, ASST Spedali Civili, Brescia, Italy.
¹² Pediatric Department and Centro Tettamanti-European Reference Network on Paediatric Cancer, European Reference Network on Haematological Diseases, and European Reference Network on Hereditary Metabolic Disorders, University of Milano-Bicocca-Fondazione MBBM, Monza, Italy.
¹³ Department of Infectious Diseases, San Gerardo Hospital, University of Milano-Bicocca, Monza, Italy.
¹⁴ Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Md.
¹⁵ Clinic of Infectious Diseases, Azienda Ospedaliero-Universitaria Consorziale Policlinico di Bari, University of Bari, Bari, Italy.
¹⁶ Hygiene Section, Department of Interdisciplinary Medicine, University of Bari Aldo Moro, Bari, Italy.
¹⁷ Department of Medical and Surgical Sciences, Section of Infectious Diseases, University of Foggia, Foggia, Italy.
¹⁸ Department of Clinical, Surgical, Diagnostic and Pediatric Sciences, University of Pavia, Pavia, Italy; Pediatric Clinic, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
¹⁹ Molecular Development of the Immune System Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Md.
²⁰ Bioinformatics and Computational Biosciences Branch, Office of Cyber Infrastructure and Computational Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Md.
²¹ Center for Immuno-Oncology, National Cancer Institute, National Institutes of Health, Bethesda, Md.
²² Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Md.
²³ Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Md.
²⁴ Laboratory of Clinical Immunology and Microbiology National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Md. Electronic address: luigi.notarangelo2@nih.gov.

PMID: 38154666
DOI: 10.1016/j.jaci.2023.12.011

Abstract

Background: Functional T-cell responses are essential for virus clearance and long-term protection after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, whereas certain clinical factors, such as older age and immunocompromise, are associated with worse outcome.

Objective: We sought to study the breadth and magnitude of T-cell responses in patients with coronavirus disease 2019 (COVID-19) and in individuals with inborn errors of immunity (IEIs) who had received COVID-19 mRNA vaccine.

Methods: Using high-throughput sequencing and bioinformatics tools to characterize the T-cell receptor β repertoire signatures in 540 individuals after SARS-CoV-2 infection, 31 IEI recipients of COVID-19 mRNA vaccine, and healthy controls, we quantified HLA class I- and class II-restricted SARS-CoV-2-specific responses and also identified several HLA allele-clonotype motif associations in patients with COVID-19, including a subcohort of anti-type 1 interferon (IFN-1)-positive patients.

Results: Our analysis revealed that elderly patients with COVID-19 with critical disease manifested lower SARS-CoV-2 T-cell clonotype diversity as well as T-cell responses with reduced magnitude, whereas the SARS-CoV-2-specific clonotypes targeted a broad range of HLA class I- and class II-restricted epitopes across the viral proteome. The presence of anti-IFN-I antibodies was associated with certain HLA alleles. Finally, COVID-19 mRNA immunization induced an increase in the breadth of SARS-CoV-2-specific clonotypes in patients with IEIs, including those who had failed to seroconvert.

Conclusions: Elderly individuals have impaired capacity to develop broad and sustained T-cell responses after SARS-CoV-2 infection. Genetic factors may play a role in the production of anti-IFN-1 antibodies. COVID-19 mRNA vaccines are effective in inducing T-cell responses in patients with IEIs.

Keywords: COVID-19; COVID-19 mRNA vaccine; SARS-CoV-2; T-cell receptor repertoire; anti–type 1 interferon antibodies; inborn errors of immunity.

Published by Elsevier Inc.