Global patterns of antigen receptor repertoire disruption across adaptive immune compartments in COVID-19

Joseph, Magdalene; Wu, Yin; Dannebaum, Richard; Rubelt, Florian; Zlatareva, Iva; Lorenc, Anna; Du, Zhipei Gracie; Davies, Daniel; Kyle-Cezar, Fernanda; Das, Abhishek; Gee, Sarah; Graham, Carl; Dilduz, Telman; Bermejo, Clara; Lin, Hai; Asgharian, Hosseinali; Laing, Adam; Barrio, Irene del Molino del; Monin-Aldama, Leticia; Muñoz‐Ruiz, Miguel; McKenzie, Duncan R.; Hayday, Thomas; Kamdar, Shraddha; Davis, Richard P.; Sofra, Vasiliki; Cano, Florencia; Theodoridis, Efstathios; Martinez, Lauren; Merrick, Blair; Bisnauthsing, Karen; Brooks, Kate; Edgeworth, Jonathan D; Cason, John; Mant, Christine; Doores, Katie J.; Vantourout, Pierre; Berka, Jan; Hayday, Adrian

doi:10.1073/pnas.2201541119

Cited by 15 publications

(17 citation statements)

References 67 publications

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“…15 While no differences in Vd1 + T cells have been identified, a recent study showed that TCRd1 + (TRDV1) CDR3 sequences showed evidence of clonal focusing in COVID-19 patients aged > 50 years. 16 cd T cell subsets have been implicated in controlling other viral infections such as CMV and severe acute respiratory syndrome (SARS). In CMV, Vd1 + T cells expanded rapidly and undergo cd TCR clonotype expansion upon infection in both stem cell 17 and kidney [18][19][20][21] transplantation settings and have been implicated in the resolution of CMV infection.…”

Section: Introductionmentioning

confidence: 99%

Circulating effector γδ T cell populations are associated with acute coronavirus disease 19 in unvaccinated individuals

et al. 2023

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Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection causes severe coronavirus disease 2019 (COVID‐19) in a small proportion of infected individuals. The immune system plays an important role in the defense against SARS‐CoV‐2, but our understanding of the cellular immune parameters that contribute to severe COVID‐19 disease is incomplete. Here, we show that populations of effector γδ T cells are associated with COVID‐19 in unvaccinated patients with acute disease. We found that circulating CD27negCD45RA+CX3CR1+ Vδ1effector cells expressing Granzymes (Gzms) were enriched in COVID‐19 patients with acute disease. Moreover, higher frequencies of GzmB+ Vδ2+ T cells were observed in acute COVID‐19 patients. SARS‐CoV‐2 infection did not alter the γδ T cell receptor repertoire of either Vδ1+ or Vδ2+ subsets. Our work demonstrates an association between effector populations of γδ T cells and acute COVID‐19 in unvaccinated individuals.

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Section: Introductionmentioning

confidence: 99%

Circulating effector γδ T cell populations are associated with acute coronavirus disease 19 in unvaccinated individuals

et al. 2023

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“…We collected immune repertoire sequencing data for a total of 285 individuals, comprising 152 healthy individuals and 133 subjects with disease (79 COVID-19 patients and 54 autoimmune hepatitis patients) from 5 independent datasets ( 15 , 16 , 18 – 20 ). All studies from which the sequence information was gathered performed targeted immune receptor sequencing.…”

Section: Resultsmentioning

confidence: 99%

“…We conducted replication and validation analyses on a separate study with 43 healthy controls and 32 COVID-19 patients ( 20 ). In this study, genomic DNA from peripheral blood mononuclear cells were isolated to generate immune receptor libraries using the immunoPETE protocol from Roche Sequencing Solutions, providing sequence information for an average of 22,834 T cell clonotypes and 9,141 B cell clonotypes per individual.…”

Section: Methodsmentioning

confidence: 99%

Exploration of shared features of B cell receptor and T cell receptor repertoires reveals distinct clonotype clusters

et al. 2022

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Although B cells and T cells are integral players of the adaptive immune system and act in co-dependent ways to orchestrate immune responses, existing methods to study the immune repertoire have largely focused on separate analyses of B cell receptor (BCR) and T cell receptor (TCR) repertoires. Based on our hypothesis that the shared history of immune exposures and the shared cellular machinery for recombination result in similarities between BCR and TCR repertoires in an individual, we examine any commonalities and interrelationships between BCR and TCR repertoires. We find that the BCR and TCR repertoires have covarying clonal architecture and diversity, and that the pattern of correlations appears to be altered in immune-mediated diseases. Furthermore, hierarchical clustering of public B and T cell clonotypes in both health and disease based on correlation of clonal proportion revealed distinct clusters of B and T cell clonotypes that exhibit increased sequence similarity, share motifs, and have distinct amino acid characteristics. Our findings point to common principles governing memory formation, recombination, and clonal expansion to antigens in B and T cells within an individual. A significant proportion of public BCR and TCR repertoire can be clustered into nonoverlapping and correlated clusters, suggesting a novel way of grouping B and T cell clonotypes.

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“…With regard to cardiovascular medicine, it is desirable to know specific genetic risk factors for the development of myocarditis during COVID-19 or upon vaccination [112,[165][166][167][168][169][170][226][227][228][229][230][231][232], or for development of long COVID syndromes [191,[233][234][235][236][237][238][239]. Fortunately, SARS-CoV-2 is rather rarely causing severe myocarditis or cardiomyopathies [165][166][167][168][169][170].…”

Section: Cardiovascular Immunobiology Of Covid-19 and Long Covid Synd...mentioning

confidence: 99%

Innate Immunity in Cardiovascular Diseases – Identification of Novel Molecular Players and Targets

Poller¹,

Heidecker²,

Ammirati³

et al. 2022

Preprint

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During the past few years unexpected developments have driven studies in the field of clinical immunology. One driver of immense impact was the outbreak of a pandemic caused by the novel virus SARS-CoV-2. Excellent recent reviews address diverse aspects of immunological re-search into cardiovascular diseases. Here, we specifically focus on selected studies taking ad-vantage of advanced state-of-the-art molecular genetic methods ranging from genome-wide epi/transcriptome mapping and variant scanning to optogenetics and chemogenetics. First, we discuss emerging clinical relevance of advanced diagnostics for cardiovascular diseases - includ-ing those associated with COVID-19 - with a focus on the role of inflammation in cardiomyopa-thies and arrhythmias. Second, we consider newly identified immunological interactions at or-gan and systems level which affect cardiovascular pathogenesis. Thus, studies into immune in-fluences arising from the intestinal system are moving towards therapeutic exploitation. Fur-ther, powerful new research tools have enabled novel insight into brain – immune system inter-actions at unprecedented resolution. This latter line of investigation emphasizes the strength of influence of emotional stress - acting through defined brain regions - upon viral and cardiovas-cular disorders. Several challenges need to be overcome before the full impact of these far-reaching new findings will hit the clinical arena.

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Global patterns of antigen receptor repertoire disruption across adaptive immune compartments in COVID-19

Cited by 15 publications

References 67 publications

Circulating effector γδ T cell populations are associated with acute coronavirus disease 19 in unvaccinated individuals

Circulating effector γδ T cell populations are associated with acute coronavirus disease 19 in unvaccinated individuals

Exploration of shared features of B cell receptor and T cell receptor repertoires reveals distinct clonotype clusters

Innate Immunity in Cardiovascular Diseases – Identification of Novel Molecular Players and Targets

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