Prevalence and Gene Characteristics of Antibodies with Cofactor-induced HIV-1 Specificity

Lecerf, Maxime; Scheel, Tobias; Pashov, Anastas; Jarossay, Annaëlle; Ohayon, Delphine; Planchais, Cyril; Mesnage, Stéphane; Berek, Claudia; Kaveri, Srini V.; Lacroix‐Desmazes, Sébastien; Dimitrov, Jordan D.

doi:10.1074/jbc.m114.618124

Cited by 30 publications

(40 citation statements)

References 66 publications

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“…Likewise, exposure of purified pooled human IgG to haem leads to the acquisition of a considerable reactivity to many prototypical autoantigens used as targets for the diagnosis of autoimmune diseases [100][101][102] . Further investigations revealed that the interaction of human antibodies with haem induces a diversification in reactivity not only toward autoantigens but also toward pathogen-derived antigens 95,103,104 . It is noteworthy that binding affinities for the antigens recognized by haem-exposed IgG are substantial 105 .…”

Section: [H2] Use Of Non-protein Cofactorsmentioning

confidence: 99%

“…Binding analyses of repertoires of human monoclonal antibodies revealed that, depending on the studied antigen, the fraction of IgG that acquire novel antigen-binding specificities after contact with haem ranges between 9 and 24% 103,104 . Of note, the repertoire analyses demonstrated that haem-sensitive IgG had significantly lower number of somatic mutations in the genes encoding their V regions as compared to IgG that did not change their specificity upon exposure to haem 103,104 .…”

Section: [H2] Use Of Non-protein Cofactorsmentioning

confidence: 99%

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Breaking the law: unconventional strategies for antibody diversification

et al. 2019

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Antibodies are an essential component of adaptive immunity. A typical antibody repertoire comprises an enormous diversity of antigen-binding specificities, which are generated by the genetic processes of recombination and mutation. Accumulating evidence suggests that the immune system can exploit additional strategies to diversify the repertoire of antigen specificities. These unconventional mechanisms exclusively target the antigen-binding sites of immunoglobulins and include the insertion of large amino acid sequences, post-translational modifications, conformational heterogeneity, and use of non-proteinaceous cofactor molecules. Here, we describe the different unconventional routes for diversification of antibody specificities. Furthermore, we highlight how the immune system has a much greater level of adaptability and plasticity than previously anticipated, which goes far beyond that encoded in the genome or generated by the acquisition of somatic mutations.

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Section: [H2] Use Of Non-protein Cofactorsmentioning

confidence: 99%

Section: [H2] Use Of Non-protein Cofactorsmentioning

confidence: 99%

Breaking the law: unconventional strategies for antibody diversification

et al. 2019

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“…Aside from inducing a pro‐thrombotic phenotype and activating complement heme inhibits ADAMTS‐13 activity, or activation of coagulation cascade . It also modifies the spectrum of recognized antigens by a particular fraction of immunoglobulins in the circulation . Thus, hemolysis is a supplemental actor, which participates in the definition of TMA, may act as a secondary hit, since others events had preceded it to induce the initial thrombus formation, causing erythrocytes rupture and heme release.…”

Section: Endothelial Cells As a Target In Ahusmentioning

confidence: 99%

“…204 It also modifies the spectrum of recognized antigens by a particular fraction of immunoglobulins in the circulation. 201,205 Thus, hemolysis is a supplemental actor, which participates in the definition of TMA, may act as a secondary hit, since others events had preceded it to induce the initial thrombus formation, causing erythrocytes rupture and heme release. By amplifying complement activation and prothrombogenic traits, heme creates a positive feedback loop that exacerbates endothelial activation.…”

Section: Redundancy Of the Aggression Makes The Diseasementioning

confidence: 99%

Endothelial cells: source, barrier, and target of defensive mediators

Roumenina

Rayes

Frimat

et al. 2016

Immunological Reviews

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Endothelium is strategically located at the interface between blood and interstitial tissues, placing thus endothelial cell as a key player in vascular homeostasis. Endothelial cells are in a dynamic equilibrium with their environment and constitute concomitantly a source, a barrier, and a target of defensive mediators. This review will discuss the recent advances in our understanding of the complex crosstalk between the endothelium, the complement system and the hemostasis in health and in disease. The first part will provide a general introduction on endothelial cells heterogeneity and on the physiologic role of the complement and hemostatic systems. The second part will analyze the interplay between complement, hemostasis and endothelial cells in physiological conditions and their alterations in diseases. Particular focus will be made on the prototypes of thrombotic microangiopathic disorders, resulting from complement or hemostasis dysregulation-mediated endothelial damage: atypical hemolytic uremic syndrome and thrombotic thrombocytopenic purpura. Novel aspects of the pathophysiology of the thrombotic microangiopathies will be discussed.

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“…Therefore, heme as a key player in initiating or mediating distinct processes in connection with a viral infection needs to be considered as well. This can be exemplified with the interaction of heme with e.g., Zika, Chikungunya, and HIV-1 viruses (Gupta et al, 2015;Lecerf et al, 2015;Assunção-Miranda et al, 2016;Neris et al, 2018).…”

Section: Resultsmentioning

confidence: 99%

Unravelling the debate on heme effects in COVID-19 infections

Hopp

Domingo‐Fernándéz

Gadiya

et al. 2020

Preprint

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The SARS-CoV-2 outbreak was recently declared a worldwide pandemic. Infection triggers the respiratory tract disease COVID-19, which is accompanied by serious changes of clinical biomarkers such as hemoglobin and interleukins. The same parameters are altered during hemolysis, which is characterized by an increase in labile heme. We present two approaches that aim at analyzing a potential link between available heme and COVID-19 pathogenesis. Four COVID-19 related proteins, i.e. the host cell proteins ACE2 and TMPRSS2 as well as the viral protein 7a and S protein, were identified as potential heme binders. We also performed a detailed analysis of the common pathways induced by heme and SARS-CoV-2 by superimposition of knowledge graphs covering heme biology and COVID-19 pathophysiology. Herein, focus was laid on inflammatory pathways, and distinct biomarkers as the linking elements. Finally, the results substantially improve our understanding of COVID-19 infections and disease progression of patients with different clinical backgrounds and expand the diagnostic and treatment options.

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Prevalence and Gene Characteristics of Antibodies with Cofactor-induced HIV-1 Specificity

Cited by 30 publications

References 66 publications

Breaking the law: unconventional strategies for antibody diversification

Breaking the law: unconventional strategies for antibody diversification

Endothelial cells: source, barrier, and target of defensive mediators

Unravelling the debate on heme effects in COVID-19 infections

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