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

被引：5

作者：

Delmonte, Ottavia M. ^{[1
]}

Oguz, Cihan ^{[2
]}

Dobbs, Kerry ^{[1
]}

Myint-Hpu, Katherine ^{[1
]}

Palterer, Boaz ^{[1
]}

Abers, Michael S. ^{[1
]}

Draper, Deborah ^{[1
]}

Truong, Meng ^{[1
]}

Kaplan, Ian M. ^{[3
]}

Gittelman, Rachel M. ^{[3
]}

Zhang, Yu ^{[1
]}

Rosen, Lindsey B. ^{[1
]}

Snow, Andrew L. ^{[1
,4
]}

Dalgard, Clifton L. ^{[5
,6
]}

Burbelo, Peter D. ^{[7
]}

Imberti, Luisa ^{[8
]}

Sottini, Alessandra ^{[8
]}

Quiros-Roldan, Eugenia ^{[9
]}

Castelli, Francesco ^{[9
]}

Rossi, Camillo ^{[10
]}

Brugnoni, Duilio ^{[11
]}

Biondi, Andrea ^{[12
,13
,14
]}

Bettini, Laura Rachele ^{[12
,13
,14
]}

D'Angio, Mariella ^{[12
,13
,14
]}

Bonfanti, Paolo ^{[15
]}

Anderson, Megan, V ^{[16
]}

Saracino, Annalisa ^{[17
]}

Chironna, Maria ^{[18
]}

Di Stefano, Mariantonietta ^{[19
]}

Fiore, Jose Ramon ^{[19
]}

Santantonio, Teresa ^{[19
]}

Castagnoli, Riccardo ^{[20
,21
]}

Marseglia, Gian Luigi ^{[20
,21
]}

Magliocco, Mary ^{[22
]}

Bosticardo, Marita ^{[1
]}

Pala, Francesca ^{[1
]}

Shaw, Elana ^{[1
]}

Matthews, Helen ^{[22
]}

Weber, Sarah E. ^{[22
]}

Xirasagar, Sandhya ^{[23
]}

Barnett, Jason ^{[23
]}

Oler, Andrew J. ^{[23
]}

Dimitrova, Dimana ^{[24
]}

Bergerson, Jenna R. E. ^{[1
]}

Mcdermott, David H. ^{[25
]}

Rao, V. Koneti ^{[1
]}

Murphy, Philip M. ^{[25
]}

Holland, Steven M. ^{[1
]}

Lisco, Andrea ^{[16
]}

Su, Helen C. ^{[1
]}

机构：

[1] Natl Inst Allergyand Infect Dis, NIH, Res Technol Branch, Lab Clin Immunol & Microbiol, Bethesda, MD USA

[2] Natl Inst Allergyand Infect Dis, NIH, Res Technol Branch, Integrated Data Sci Sect, Bethesda, MD USA

[3] Adapt Biotechnol, Seattle, WA USA

[4] Uniformed Serv Univ Hlth Sci, Dept Pharmacol & Mol Therapeut, Bethesda, MD USA

[5] Uniformed Serv Univ Hlth Sci, Dept Anat Physiol & Genet, Bethesda, MD USA

[6] Uniformed Serv Univ Hlth Sci, Amer Genome Ctr, Bethesda, MD USA

[7] Natl Inst Dent & Craniofacial Res, NIH, Adeno Associated Virus Biol Sect, Bethesda, MD USA

[8] Univ Brescia, Sect Microbiol, Brescia, Italy

[9] Univ Brescia, Dept Infect & Trop Dis, Brescia, Italy

[10] Direzione Sanit, Turin, Italy

[11] ASST Spedali Civili, Lab Anal Chim Clin, Brescia, Italy

[12] Univ Milano Bicocca, Fdn MBBM, Pediat Dept, European Reference Network Haematol Dis, Monza, Italy

[13] Univ Milano Bicocca, Fdn MBBM, Ctr Tettamanti, European Reference Network Paediat Canc,European R, Monza, Italy

[14] Univ Milano Bicocca, Fdn MBBM, European Reference Network Hereditary Metab Disord, Monza, Italy

[15] Univ Milano Bicocca, San Gerardo Hosp, Dept Infect Dis, Monza, Italy

[16] Natl Inst Allergy & Infect Dis, NIH, Lab Immunoregulat, Bethesda, MD USA

[17] Univ Bari, Clin Infect Dis, Azienda Osped Univ Consorziale Policlin di Bari, Bari, Italy

[18] Univ Bari Aldo Moro, Dept Interdisciplinary Med, Hyg Sect, Bari, Italy

[19] Univ Foggia, Dept Med & Surg Sci, Sect Infect Dis, Foggia, Italy

[20] Univ Pavia, Dept Clin Surg Diagnost & Pediat Sci, Pavia, Italy

[21] Fdn IRCCS Policlin San Matteo, Pediat Clin, Pavia, Italy

[22] Natl Inst Allergy & Infect Dis, Mol Dev Immune Syst Sect, Lab Immune Syst Biol, Bethesda, MD USA

[23] Natl Inst Allergy & Infect Dis, Bioinformat & Computat Biosci Branch, Off Cyber Infrastructure & Computat Biol, Bethesda, MD USA

[24] NCI, Ctr Immunooncol, Bethesda, MD USA

[25] Natl Inst Allergy & Infect Dis, Lab Mol Immunol, Bethesda, MD USA

[26] Natl Inst Allergy & Infect Dis, NIH, Lab Infect Dis, Bethesda, MD USA

来源：

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY | 2024年 / 153卷 / 06期

基金：

美国国家卫生研究院;

关键词：

COVID-19; SARS-CoV-2; T-cell receptor repertoire; inborn errors of immunity; COVID-19 mRNA vaccine; anti-type 1 interferon antibodies; ANTIBODY-RESPONSES; NEURAL-NETWORKS; COVID-19; IMMUNITY; EPITOPES; AUTOANTIBODIES; INFLAMMATION; CANCER;

D O I：

10.1016/j.jaci.2023.12.011

中图分类号：

R392 [医学免疫学];

学科分类号：

100102 ;

摘要：

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 b repertoire signatures in 540 individuals after SARS-CoV-2 infection, 31 IEI recipients of COVID-19 mRNA vaccine, and healthy controls, we quantified LILA class I- and class II-restricted SARS-CoV-2- specific responses and also identified several LILA 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 LILA class I- and class II- restricted epitopes across the viral proteome. The presence of anti-IFN-I antibodies was associated with certain LILA 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.

引用

页码：1655 / 1667

页数：13

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