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Molecular characterization of a cross-reactive idiotope on human immunoglobulins utilizing the VH4-21 gene segment

The anti-idiotypic (anti-Id) antibody (Ab) 9G4 binds a cross-reactive idiotope (CRI) present in a select group of human autoantibodies. This Id has been localized to the portion of immunoglobulin (Ig) heavy (H) chains encoded by the VH4-21 gene segment, a member of the human VH4 family. This gene se...

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Detalles Bibliográficos
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 1993
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2191190/
https://www.ncbi.nlm.nih.gov/pubmed/8376944
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description The anti-idiotypic (anti-Id) antibody (Ab) 9G4 binds a cross-reactive idiotope (CRI) present in a select group of human autoantibodies. This Id has been localized to the portion of immunoglobulin (Ig) heavy (H) chains encoded by the VH4-21 gene segment, a member of the human VH4 family. This gene segment is utilized by essentially all cold agglutinin (CA) Abs with I/i specificity isolated from patients with CA disease stemming from chronic lymphoproliferative disorders. In this study, mutational analysis of a CA has been used to determine the structural basis for 9G4 binding to Abs utilizing the VH4-21 gene segment. Recombinant CA H chain mutants were produced and their 9G4 reactivity determined. Mutants were generated by exchanging VH4-21 sequences in the FR1, CDR1, and CDR2 with corresponding sequences from a closely related gene segment V71-2, a VH4 family member that is associated neither with Abs having CA activity nor with Abs that react with 9G4. The results indicate that the motif AVY at amino acid positions 23-25 in FR1 defines the 9G4 idiotope. Reaction of these recombinant Abs with a polyclonal rabbit anti-CA antiserum absorbed to render it specific for a CA CRI also maps predominantly to FR1. These findings indicate that the solvent-exposed FR1 plays an important role in eliciting an immune response to Igs.
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spelling pubmed-21911902008-04-16 Molecular characterization of a cross-reactive idiotope on human immunoglobulins utilizing the VH4-21 gene segment J Exp Med Articles The anti-idiotypic (anti-Id) antibody (Ab) 9G4 binds a cross-reactive idiotope (CRI) present in a select group of human autoantibodies. This Id has been localized to the portion of immunoglobulin (Ig) heavy (H) chains encoded by the VH4-21 gene segment, a member of the human VH4 family. This gene segment is utilized by essentially all cold agglutinin (CA) Abs with I/i specificity isolated from patients with CA disease stemming from chronic lymphoproliferative disorders. In this study, mutational analysis of a CA has been used to determine the structural basis for 9G4 binding to Abs utilizing the VH4-21 gene segment. Recombinant CA H chain mutants were produced and their 9G4 reactivity determined. Mutants were generated by exchanging VH4-21 sequences in the FR1, CDR1, and CDR2 with corresponding sequences from a closely related gene segment V71-2, a VH4 family member that is associated neither with Abs having CA activity nor with Abs that react with 9G4. The results indicate that the motif AVY at amino acid positions 23-25 in FR1 defines the 9G4 idiotope. Reaction of these recombinant Abs with a polyclonal rabbit anti-CA antiserum absorbed to render it specific for a CA CRI also maps predominantly to FR1. These findings indicate that the solvent-exposed FR1 plays an important role in eliciting an immune response to Igs. The Rockefeller University Press 1993-10-01 /pmc/articles/PMC2191190/ /pubmed/8376944 Text en This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Articles
Molecular characterization of a cross-reactive idiotope on human immunoglobulins utilizing the VH4-21 gene segment
title Molecular characterization of a cross-reactive idiotope on human immunoglobulins utilizing the VH4-21 gene segment
title_full Molecular characterization of a cross-reactive idiotope on human immunoglobulins utilizing the VH4-21 gene segment
title_fullStr Molecular characterization of a cross-reactive idiotope on human immunoglobulins utilizing the VH4-21 gene segment
title_full_unstemmed Molecular characterization of a cross-reactive idiotope on human immunoglobulins utilizing the VH4-21 gene segment
title_short Molecular characterization of a cross-reactive idiotope on human immunoglobulins utilizing the VH4-21 gene segment
title_sort molecular characterization of a cross-reactive idiotope on human immunoglobulins utilizing the vh4-21 gene segment
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2191190/
https://www.ncbi.nlm.nih.gov/pubmed/8376944