Mouse monoclonal antibodies to pneumococcal C-polysaccharide backbone show restricted usage of VH-DH-JH gene segments and share the same kappa chain

Fernández-Sánchez, Alba; García-Ocaña, Marcos; Toyos, Juan R. de los

doi:10.1016/j.imlet.2009.02.012

Cited by 5 publications

(2 citation statements)

References 35 publications

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“…This is an important area to advance understanding in autoimmunity, immunity against infectious diseases and immunization. Studies of the BCR repertoire generated in response to specific antigens such as bacterial polysaccharides (14-16), viral glycoproteins (17-19) and autoimmune antigens (20) have used small numbers of immortalized B cell lines and suggested that genetically diverse individuals utilized similar combinations of heavy chain VDJ segments in response to a given antigen. However there is some evidence that VDJ gene segment usage may be relatively independent of antigen specificity supported by the fact that BCR sequences that differ markedly in the CDR3 sequence can have the same V(D)J usage (J. Trück, unpublished observations).…”

Section: Introductionmentioning

confidence: 99%

Identification of Antigen-Specific B Cell Receptor Sequences Using Public Repertoire Analysis

Trück

Ramasamy

Galson

et al. 2015

The Journal of Immunology

114

105

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High-throughput sequencing allows detailed study of the B cell receptor (BCR) repertoire post-immunization but it remains unclear to what extent the de novo identification of antigen-specific sequences from the total BCR repertoire is possible. A Hib-MenC-TT conjugate vaccine containing H. influenzae type b (Hib) and group C meningococcal (MenC) polysaccharides as well as tetanus toxoid (TT) was used to investigate the BCR repertoire of adult humans following immunization and test the hypothesis that public or convergent repertoire analysis could identify antigen specific sequences. A number of antigen-specific BCR sequences have previously been reported for Hib and TT which made a vaccine containing these 2 antigens an ideal immunological stimulus. Analysis of identical complementarity determining region (CDR)3 amino acid (AA) sequences that were shared by individuals in the post-vaccine repertoire identified a number of known Hib-specific sequences but only one previously described TT sequence. The extension of this analysis to non-identical but highly similar CDR3 AA sequences revealed a number of other TT-related sequences. The anti-Hib avidity index post-vaccination was strongly correlated with the relative frequency of Hib-specific sequences, indicating that the post-vaccination public BCR repertoire may be related to more conventional measures of immunogenicity correlating with disease protection. Analysis of public BCR repertoire provided evidence of convergent BCR evolution in individuals exposed to the same antigens. If this finding is confirmed, the public repertoire could be used for rapid and direct identification of protective antigen-specific BCR sequences from peripheral blood.

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Section: Introductionmentioning

confidence: 99%

Identification of Antigen-Specific B Cell Receptor Sequences Using Public Repertoire Analysis

Trück

Ramasamy

Galson

et al. 2015

The Journal of Immunology

114

105

View full text Add to dashboard Cite

show abstract

“…It was surprising to observe that all these mAbs were characterized by a highly restricted V gene usage and VH/VL pairing. Such restrictions in V gene usage or in VH/VL pairing have been reported in antibodies against certain allergens (Persson et al, 2008), haptens (Diaw et al, 1999), viral (McLean et al, 2005; Zhang et al, 2006), and bacterial antigens (Fernández-Sánchez et al, 2009). It has been postulated that structural constraints could be involved in this phenomenon (Hougs et al, 1999; Andersen et al, 2007; Thomson et al, 2008).…”

Section: Discussionmentioning

confidence: 88%

Restricted V gene usage and VH/VL pairing of mouse humoral response against the N-terminal immunodominant epitope of the amyloid β peptide

Robert

Lefranc

Ghochikyan

et al. 2010

Molecular Immunology

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Over the last decade, the potential of antibodies as therapeutic strategies to treat Alzheimer’s disease (AD) has been growing, based on successful experimental and clinical trials in transgenic mice. Despite, undesirable side effects in humans using an active immunization approach, immunotherapy still remains one of the most promising treatments for AD. In this study, we analyzed the V genes of twelve independently isolated monoclonal antibodies raised against the N-terminal immunodominant epitope of the amyloid β peptide (Aβ or A beta). Surprisingly, we found a high and unusual level of restriction in the VH/VL pairing of these antibodies. Moreover, these antibodies mostly differ in their heavy chain complementary determining region 3 (HCDR3) and the residues in the antibodies which contact Aβ are already present in the germline V-genes. Based on these observations and or co-crystal structures of antibodies with Aβ, the aim of the current study was to better understand the role of antibody V-domains, HCDR3 regions, key contact residue (H58) and germline encoded residues in Aβ recognition. For that purpose, we designed and produced a range of recombinant Fab constructs. All the Fabs were tested and compared by surface plasmon resonance on Aβ1–16, Aβ1–42 high molecular weight and Aβ1–42 low molecular weight soluble oligomers. Although all the Fabs recognized the Aβ1–16 peptide and the Aβ1–42 high molecular weight soluble oligomers, they did not bind the Aβ1–42 low molecular weight soluble oligomers. Furthermore, we demonstrated that: (1) an aromatic residue at position H58 in the antibody is essential in the recognition of Aβ and (2) Fabs based on germline V-genes bind to Aβ monomers with a low affinity. These findings may have important implications in designing more effective therapeutic antibodies against Aβ.

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ELISA for detection of variant rabbit haemorrhagic disease virus RHDV2 antigen in liver extracts

Dalton

Podadera

Granda

et al. 2018

Journal of Virological Methods

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Mouse monoclonal antibodies to pneumococcal C-polysaccharide backbone show restricted usage of VH-DH-JH gene segments and share the same kappa chain

Cited by 5 publications

References 35 publications

Identification of Antigen-Specific B Cell Receptor Sequences Using Public Repertoire Analysis

Identification of Antigen-Specific B Cell Receptor Sequences Using Public Repertoire Analysis

Restricted V gene usage and VH/VL pairing of mouse humoral response against the N-terminal immunodominant epitope of the amyloid β peptide

ELISA for detection of variant rabbit haemorrhagic disease virus RHDV2 antigen in liver extracts

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