IMGT(R), the international ImMunoGeneTics information system(R)

Lefranc, Marie‐Paule; Giudicelli, Véronique; Ginestoux, Chantal; Jabado-Michaloud, Joumana; Folch, Géraldine; Bellahcene, Fatena; Wu, Yanyan; Gemrot, Elodie; Brochet, Xavier; Lane, Jerome C.; Regnier, Laëtitia; Ehrenmann, François; Lefranc, Gérard; Duroux, Patrice

doi:10.1093/nar/gkn838

Cited by 832 publications

(647 citation statements)

References 38 publications

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“…Recombinant DENV--2 FGA02 sE (1--395) was cloned into a vector pMT/BIP/V5--His with a C--terminal His--tag and produced in Drosophila S2 cells 33 10/300 GL column equilibrated in 50mM Tris pH8, 500mM NaCl.…”

Section: Methodsmentioning

confidence: 99%

“…The Ab sequences were analyzed by Abysis (www.bioinf.org.uk/software) and IMGT (www.imgt.org) 33 websites for mapping CDR/FWR regions according to Kabat 32 and IMGT 33 conventions, respectively. The analysis of the putative germline and somatic maturation events was done with the IMGT website (www.imgt.org).…”

Section: Analysis Of the Atomic Models And Illustrationsmentioning

confidence: 99%

See 1 more Smart Citation

Recognition determinants of broadly neutralizing human antibodies against dengue viruses

Rouvinski

Guardado-Calvo

Barba-Spaeth

et al. 2015

Nature

303

339

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2Dengue disease is caused by four different flavivirus 1 serotypes, which infect 390 million people yearly with 25% symptomatic cases 2 and for which no licensed vaccine is available. Recent phase III vaccine trials showed partial protection, and in particular no protection for dengue virus serotype 2 (DENV--2) 3,4 . Structural studies so far have characterized only epitopes recognized by serotype specific human antibodies 5,6 . We recently isolated human antibodies potently neutralizing all four DENV serotypes 7 . Here we describe the X--ray structures of four of these broadly neutralizing antibodies (bnAbs) in complex with the envelope glycoprotein E from DENV--2, revealing that the recognition determinants are at a serotype conserved site at the E dimer interface, including the exposed main chain of the E fusion loop 8 and the two conserved glycan chains.This "E--dimer dependent epitope" (EDE) is also the binding site for the viral glycoprotein prM during virus maturation in the secretory pathway of the infected cell 9 , explaining its conservation across serotypes and highlighting an Achilles heel of the virus with respect to antibody neutralization. These findings will be instrumental for devising novel immunogens to protect simultaneously against all four serotypes of dengue virus.Exposed at the surface of infectious mature DENV particles, protein E is the sole target of neutralizing antibodies. It displays an icosahedral arrangement in which 90 E dimers completely coat the viral surface 10,11 and which is sensitive to the environmental pH. Upon entry of DENV into cells via receptor--mediated endocytosis, the acidic 3 endosomal environment triggers an irreversible fusogenic conformational change in E that leads to fusion of viral and endosomal membranes 1 . The structure of the isolated E dimer has been determined by X--ray crystallography using the soluble ectodomain (sE) 8,12 . Protein E is relatively conserved, displaying about 65% amino acid sequence identity when comparing the most distant DENV serotypes. In particular, there are two conserved N--linked glycosylation sites at positions N67 and N153. To examine its interaction with the antibodies, we selected four highly potent bnAbs identified in the accompanying work: 747(4) A11 and 747 B7 (EDE2 group, requiring glycosylation at position N153 for efficient binding) and 752--2 C8 and 753(3) C10 (EDE1 group, binding regardless of the glycosylation at N153) 7 -referred to as A11, B7, C8 and C10 from hereon. The EDE2 bnAbs were isolated from the same patient (who had a secondary infection with DENV--2), and are somatic variants of the same IgG clone, derived from the IGHV3--74 and IGLV2--23 germ lines. The heavy chain has a very long (26 amino acids, IMGT convention) complementarity--determining region 3 (CDR H3). The EDE1 bnAbs were isolated from different patients and derive from (EDE1 C8, the patient appeared to have a primary infection of undetermined serotype) and IGHV1--3* and IGLV2--14 (EDE1 C10, from a patient with secondary DENV--1 infecti...

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Section: Methodsmentioning

confidence: 99%

Section: Analysis Of the Atomic Models And Illustrationsmentioning

confidence: 99%

Recognition determinants of broadly neutralizing human antibodies against dengue viruses

Rouvinski

Guardado-Calvo

Barba-Spaeth

et al. 2015

Nature

303

339

View full text Add to dashboard Cite

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“…Mutation analysis of the V region sequences were performed using the V Quest software of the international ImMunoGeneTics information system (IMGT, www.imgt.org; Ref. 31). Fully annotated nucleotide sequences of the adventitial Ig H and L chain cDNAs are available from the European Molecular Biology Laboratory database under accession numbers HF541880-HF541920 (www.ebi.ac.uk/embl/Access/index.html).…”

Section: Plasmid Preparation and Sequencingmentioning

confidence: 99%

Characterization of Resident B Cells of Vascular Walls in Human Atherosclerotic Patients

Hamze

Desmetz

Berthe

et al. 2013

The Journal of Immunology

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Animal models of atherosclerosis suggest that B cells have contradictory protective or proatherogenic effects that are also subset and context dependent. To further understand the pathophysiology of human atheroma, we characterized local Ig production and functional properties of resident B cells in human arterial lesions. Ig repertoires were analyzed by RT-PCR in carotid endarterectomy samples. Cytokine, differentiation marker and transcription factor mRNA expression was studied on arterial wall lymphocytes isolated by laser capture microdissection. Ig sequence analysis revealed that individual samples each contained a limited number of B cell clones. Functional α and γ mRNAs made up the majority of H chain mRNAs in the adventitia. Clonal evolution of Ig V regions, expression of activation-induced cytidine deaminase, clonal H chain switch, and an inverted λ/κ ratio of Ig L chain usage indicated that a local differentiation process was taking place in arterial walls. Clonotypic markers revealed different plaque and adventitia Ig repertoires and a B cell recirculation between adventitia and draining lymph nodes. Microdissected mononuclear cells had an activated phenotype expressing IL-6, GM-CSF, and TNF-α, whereas IL-2, IL-4, IL-10, M-CSF, and IFN-γ were not detected. Adventitial oligoclonal resident B cells of atherosclerotic patients are mainly mature B2 (conventional) CD20− plasmablasts lacking markers of terminal differentiation to plasma cell (CD138 and Blimp-1). They present hallmarks of Ag-driven maturation and could act on inflammation and disease progression directly or by promoting polarization of other immune cells.

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“…The germline family of light chain or heavy chain was obtained by aligning the corresponding sequences to an in-house database of sequences obtained from the IMGT database (http://www.imgt.org) where the gene family with the highest similarity to the query sequences was assigned. 49 The length of the CDR in which the residue is located, referred to as ‘cdrLength’, was included as a feature. The ‘centeredness’ of the residue within the CDR was measured as a value ranging between 0 and 1 with 0 corresponding to either end of the CDR and 1 to the center of the CDR loop.…”

Section: Methodsmentioning

confidence: 99%

Prediction of methionine oxidation risk in monoclonal antibodies using a machine learning method

Sankar¹,

Hoi²,

Yuan

et al. 2018

mAbs

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Monoclonal antibodies (mAbs) have become a major class of protein therapeutics that target a spectrum of diseases ranging from cancers to infectious diseases. Similar to any protein molecule, mAbs are susceptible to chemical modifications during the manufacturing process, long-term storage, and in vivo circulation that can impair their potency. One such modification is the oxidation of methionine residues. Chemical modifications that occur in the complementarity-determining regions (CDRs) of mAbs can lead to the abrogation of antigen binding and reduce the drug’s potency and efficacy. Thus, it is highly desirable to identify and eliminate any chemically unstable residues in the CDRs during the therapeutic antibody discovery process. To provide increased throughput over experimental methods, we extracted features from the mAbs’ sequences, structures, and dynamics, used random forests to identify important features and develop a quantitative and highly predictive in silico methionine oxidation model.

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IMGT(R), the international ImMunoGeneTics information system(R)

Cited by 832 publications

References 38 publications

Recognition determinants of broadly neutralizing human antibodies against dengue viruses

Recognition determinants of broadly neutralizing human antibodies against dengue viruses

Characterization of Resident B Cells of Vascular Walls in Human Atherosclerotic Patients

Prediction of methionine oxidation risk in monoclonal antibodies using a machine learning method

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