Molecular mimicry of the unidentified antigen of myeloma antibody IgE-ND

Thurnheer, M. Christine; Zuercher, Adrian W.; Miescher, Sylvia; Rudolf, Michael P.; Vogel, Monique; Stadler, Beda M.

doi:10.1002/(sici)1521-4141(199909)29:09<2676::aid-immu2676>3.0.co;2-o

Cited by 4 publications

(4 citation statements)

References 46 publications

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“…There have been several published attempts to identify antigens for multiple myeloma (MM) paraproteins by probing paraproteins with combinatorial peptide libraries. [1][2][3][4] The investigators tried to link the experimentally determined peptide epitopes with entries in the protein database. However, the published peptide sequences that were identified were insufficiently informative or accurate to yield meaningful database hits.…”

Section: Introductionmentioning

confidence: 99%

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Accurate identification of paraprotein antigen targets by epitope reconstruction

Sompuram

Bastas

Vani

et al. 2008

Blood

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We describe the first successful clinical application of a new discovery technology, epitope-mediated antigen prediction (E-MAP), to the investigation of multiple myeloma. Until now, there has been no reliable, systematic method to identify the cognate antigens of paraproteins. E-MAP is a variation of previous efforts to reconstruct the epitopes of paraproteins, with the significant difference that it provides enough epitope sequence data so as to enable successful protein database searches. We first reconstruct the para-

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Section: Introductionmentioning

confidence: 99%

“…However, the published peptide sequences that were identified were insufficiently informative or accurate to yield meaningful database hits. [1][2][3][4] No predictions from the protein database search were experimentally validated.…”

Section: Introductionmentioning

confidence: 99%

Accurate identification of paraprotein antigen targets by epitope reconstruction

Sompuram

Bastas

Vani

et al. 2008

Blood

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“…B cells producing IgE are also scarce (11,12), making their isolation and study equally difficult. Therefore, until recently, much of what was known about the structure, specificity, and molecular genetics of IgE Abs had come from the study of IgE myeloma proteins (13)(14)(15)(16). A more recent approach to the investigation of the structure and molecular genetics of IgE Abs has been the isolation and analysis of their rearranged Ig V region genes.…”

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confidence: 99%

Analysis of IgE Antibodies from a Patient with Atopic Dermatitis: Biased V Gene Usage and Evidence for Polyreactive IgE Heavy Chain Complementarity-Determining Region 3

Edwards

Brouwer

Choi

et al. 2002

The Journal of Immunology

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To better understand V gene usage, specificity, and clonal origins of IgE Abs in allergic reactions, we have constructed a combinatorial Ab library from the mRNA of an adult patient with atopic dermatitis. Sequence analysis of random clones revealed that 33% of clones used the IGHV6-1 H chain V gene segment, the only member of the VH6 gene family. IGHV6-1 is rarely used in the expressed adult repertoire; however, it is associated with fetal derived Abs. Features of the VH6 rearrangements included short complementarity-determining region 3, frequent use of IGHD7-27 D gene, and little nucleotide addition at the D-J junction. There was also a low level of mutation compared with VH1, VH3, and VH4 rearrangements. The library was expressed as phage-Fab fusions, and specific phage selected by panning on the egg allergen ovomucoid. Upon expression as soluble IgE Fabs, 12 clones demonstrated binding to ovomucoid, skim milk, and BSA by ELISA. Nucleotide sequencing demonstrated that the IGHV6-1 V gene segment encoded each of the 12 multiply reactive IgE Fabs. A cyclic peptide was designed from the complementarity-determining region 3 of several of these clones. The cyclic peptide bound both self and nonself Ags, including ovomucoid, human IgG, tetanus toxoid, and human and bovine von Willebrand factor. These results suggest that some IgE Abs may bind more than one Ag, which would have important implications for understanding the multiple sensitivities seen in conditions such as atopic dermatitis.

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“…In principle, peptide‐displaying phage particles can mimic the biological activity of nominal antigens, suggesting that the B‐cell receptor (BcR) could be targeted with peptides that bind specifically to the receptor as surrogate ligands. For example, mimotopes isolated by screening phage display libraries against a human immunoglobulin E (IgE) produced by a myeloma cell line were capable of mimicking the anaphylactogenic activity of the putative antigen recognized by the IgE HMP [37]. They induced release of cellular histamine from human basophils primed with interleukin‐3 and sensitized with the monoclonal IgE.…”

Section: Discussionmentioning

confidence: 99%

Probing the Specificity of Human Myeloma Proteins with a Random Peptide Phage Library

et al. 2003

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Human myeloma proteins (HMPs) from 10 patients with multiple myeloma (MM) were used to affinity-select peptides from a random phage-display peptide library. Binding peptides were identified for the 10 analysed antibodies (eight, immunoglobulin G (IgG), and two, immunoglobulin A (IgA)). The specificity of the binding was confirmed by competitive experiments using phages and chemically synthesized peptides. Interestingly, some phage-displayed peptides were immuno-selected with HMPs isolated from different patients. Sequence alignments and homology searches revealed a significant homology with human proteins (e.g. neural cell adhesion proteins) and pathogen-derived proteins (e.g. herpes simplex virus capsid proteins). The selected peptides could be useful as targeting agents for myeloma cells expressing surface immunoglobulins.

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Molecular mimicry of the unidentified antigen of myeloma antibody IgE-ND

Cited by 4 publications

References 46 publications

Accurate identification of paraprotein antigen targets by epitope reconstruction

Accurate identification of paraprotein antigen targets by epitope reconstruction

Analysis of IgE Antibodies from a Patient with Atopic Dermatitis: Biased V Gene Usage and Evidence for Polyreactive IgE Heavy Chain Complementarity-Determining Region 3

Probing the Specificity of Human Myeloma Proteins with a Random Peptide Phage Library

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