tetano
Editor, Senior Moderator
J Allergy Clin Immunol
. 2023 Dec 26:S0091-6749(23)02544-7.
doi: 10.1016/j.jaci.2023.12.011. Online ahead of print. Perturbations of the T-cell receptor repertoire in response to SARS-CoV-2 in immunocompetent and immunocompromised individuals
Ottavia M Delmonte[SUP] 1 [/SUP], Cihan Oguz[SUP] 2 [/SUP], Kerry Dobbs[SUP] 3 [/SUP], Katherine Myint-Hpu[SUP] 3 [/SUP], Boaz Palterer[SUP] 3 [/SUP], Michael S Abers[SUP] 3 [/SUP], Deborah Draper[SUP] 3 [/SUP], Meng Truong[SUP] 3 [/SUP], Ian M Kaplan[SUP] 4 [/SUP], Rachel M Gittelman[SUP] 4 [/SUP], Yu Zhang[SUP] 3 [/SUP], Lindsey B Rosen[SUP] 3 [/SUP], Andrew L Snow[SUP] 5 [/SUP], Clifton L Dalgard[SUP] 6 [/SUP], Peter D Burbelo[SUP] 7 [/SUP], Luisa Imberti[SUP] 8 [/SUP], Alessandra Sottini[SUP] 8 [/SUP], Eugenia Quiros-Roldan[SUP] 9 [/SUP], Francesco Castelli[SUP] 9 [/SUP], Camillo Rossi[SUP] 10 [/SUP], Duilio Brugnoni[SUP] 11 [/SUP], Andrea Biondi[SUP] 12 [/SUP], Laura Rachele Bettini[SUP] 12 [/SUP], Mariella D'Angio'[SUP] 12 [/SUP], Paolo Bonfanti[SUP] 13 [/SUP], Megan V Anderson[SUP] 14 [/SUP], Annalisa Saracino[SUP] 15 [/SUP], Maria Chironna[SUP] 16 [/SUP], Mariantonietta Di Stefano[SUP] 17 [/SUP], Jose Ramon Fiore[SUP] 17 [/SUP], Teresa Santantonio[SUP] 17 [/SUP], Riccardo Castagnoli[SUP] 18 [/SUP], Gian Luigi Marseglia[SUP] 18 [/SUP], Mary Magliocco[SUP] 19 [/SUP], Marita Bosticardo[SUP] 3 [/SUP], Francesca Pala[SUP] 3 [/SUP], Elana Shaw[SUP] 3 [/SUP], Helen Matthews[SUP] 19 [/SUP], Sarah E Weber[SUP] 19 [/SUP], Sandhya Xirasagar[SUP] 20 [/SUP], Jason Barnett[SUP] 20 [/SUP], Andrew J Oler[SUP] 20 [/SUP], Dimana Dimitrova[SUP] 21 [/SUP], Jenna R E Bergerson[SUP] 3 [/SUP], David H McDermott[SUP] 22 [/SUP], V Koneti Rao[SUP] 3 [/SUP], Philip M Murphy[SUP] 22 [/SUP], Steven M Holland[SUP] 3 [/SUP], Andrea Lisco[SUP] 14 [/SUP], Helen C Su[SUP] 3 [/SUP], Michail S Lionakis[SUP] 3 [/SUP], Jeffrey I Cohen[SUP] 23 [/SUP], Alexandra F Freeman[SUP] 3 [/SUP], Thomas M Snyder[SUP] 4 [/SUP], Justin Lack[SUP] 2 [/SUP], Luigi D Notarangelo[SUP] 24 [/SUP]
Affiliations
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.
Objectives: We studied the breadth and magnitude of the T-cell responses in COVID-19 patients and in individuals with inborn errors of immunity (IEI) who had received COVID-19 mRNA vaccine.
Methods: Utilizing high-throughput sequencing and bioinformatics tools to characterize the T-cell receptor β (TRB) repertoire signatures in 540 individuals after SARS-CoV-2 infection, 31 IEI recipients of COVID-19 mRNA vaccine, and in 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 COVID-19 patients, including a sub-cohort of anti-type I interferon (IFN-I)-positive patients.
Results: Our analysis revealed that elderly COVID-19 patients 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 IEI, 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-I antibodies. COVID-19 mRNA vaccines are effective in inducing T-cell responses in patients with IEI.
Keywords: COVID-19; COVID-19 mRNA vaccine; SARS-CoV-2; T-cell receptor repertoire; anti-type I interferon antibodies; inborn errors of immunity.
. 2023 Dec 26:S0091-6749(23)02544-7.
doi: 10.1016/j.jaci.2023.12.011. Online ahead of print. Perturbations of the T-cell receptor repertoire in response to SARS-CoV-2 in immunocompetent and immunocompromised individuals
Ottavia M Delmonte[SUP] 1 [/SUP], Cihan Oguz[SUP] 2 [/SUP], Kerry Dobbs[SUP] 3 [/SUP], Katherine Myint-Hpu[SUP] 3 [/SUP], Boaz Palterer[SUP] 3 [/SUP], Michael S Abers[SUP] 3 [/SUP], Deborah Draper[SUP] 3 [/SUP], Meng Truong[SUP] 3 [/SUP], Ian M Kaplan[SUP] 4 [/SUP], Rachel M Gittelman[SUP] 4 [/SUP], Yu Zhang[SUP] 3 [/SUP], Lindsey B Rosen[SUP] 3 [/SUP], Andrew L Snow[SUP] 5 [/SUP], Clifton L Dalgard[SUP] 6 [/SUP], Peter D Burbelo[SUP] 7 [/SUP], Luisa Imberti[SUP] 8 [/SUP], Alessandra Sottini[SUP] 8 [/SUP], Eugenia Quiros-Roldan[SUP] 9 [/SUP], Francesco Castelli[SUP] 9 [/SUP], Camillo Rossi[SUP] 10 [/SUP], Duilio Brugnoni[SUP] 11 [/SUP], Andrea Biondi[SUP] 12 [/SUP], Laura Rachele Bettini[SUP] 12 [/SUP], Mariella D'Angio'[SUP] 12 [/SUP], Paolo Bonfanti[SUP] 13 [/SUP], Megan V Anderson[SUP] 14 [/SUP], Annalisa Saracino[SUP] 15 [/SUP], Maria Chironna[SUP] 16 [/SUP], Mariantonietta Di Stefano[SUP] 17 [/SUP], Jose Ramon Fiore[SUP] 17 [/SUP], Teresa Santantonio[SUP] 17 [/SUP], Riccardo Castagnoli[SUP] 18 [/SUP], Gian Luigi Marseglia[SUP] 18 [/SUP], Mary Magliocco[SUP] 19 [/SUP], Marita Bosticardo[SUP] 3 [/SUP], Francesca Pala[SUP] 3 [/SUP], Elana Shaw[SUP] 3 [/SUP], Helen Matthews[SUP] 19 [/SUP], Sarah E Weber[SUP] 19 [/SUP], Sandhya Xirasagar[SUP] 20 [/SUP], Jason Barnett[SUP] 20 [/SUP], Andrew J Oler[SUP] 20 [/SUP], Dimana Dimitrova[SUP] 21 [/SUP], Jenna R E Bergerson[SUP] 3 [/SUP], David H McDermott[SUP] 22 [/SUP], V Koneti Rao[SUP] 3 [/SUP], Philip M Murphy[SUP] 22 [/SUP], Steven M Holland[SUP] 3 [/SUP], Andrea Lisco[SUP] 14 [/SUP], Helen C Su[SUP] 3 [/SUP], Michail S Lionakis[SUP] 3 [/SUP], Jeffrey I Cohen[SUP] 23 [/SUP], Alexandra F Freeman[SUP] 3 [/SUP], Thomas M Snyder[SUP] 4 [/SUP], Justin Lack[SUP] 2 [/SUP], Luigi D Notarangelo[SUP] 24 [/SUP]
Affiliations
- PMID: 38154666
- DOI: 10.1016/j.jaci.2023.12.011
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.
Objectives: We studied the breadth and magnitude of the T-cell responses in COVID-19 patients and in individuals with inborn errors of immunity (IEI) who had received COVID-19 mRNA vaccine.
Methods: Utilizing high-throughput sequencing and bioinformatics tools to characterize the T-cell receptor β (TRB) repertoire signatures in 540 individuals after SARS-CoV-2 infection, 31 IEI recipients of COVID-19 mRNA vaccine, and in 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 COVID-19 patients, including a sub-cohort of anti-type I interferon (IFN-I)-positive patients.
Results: Our analysis revealed that elderly COVID-19 patients 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 IEI, 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-I antibodies. COVID-19 mRNA vaccines are effective in inducing T-cell responses in patients with IEI.
Keywords: COVID-19; COVID-19 mRNA vaccine; SARS-CoV-2; T-cell receptor repertoire; anti-type I interferon antibodies; inborn errors of immunity.