Variable-region-identical antibodies differing in isotype demonstrate differences in fine specificity and idiotype

Marcela Torres, Rena May, Matthew D. Scharff, Arturo Casadevall

Research output: Contribution to journalArticle

62 Citations (Scopus)

Abstract

A central tenet of the current understanding of the relationship between Ab structure and function is that the variable region domain is solely responsible for Ag specificity. However, this view was recently challenged by the observation that families of mouse-human chimeric Abs with identical V regions demonstrate differences in fine specificity and by reports of changes in Ab Id structure with isotype switching. Here we revisited this question by evaluating the reactivity of two families of murine IgG switch variants that differed in V region usage for Cryptococcus neoformans glucuronoxylomannan, glucuronoxylomannan peptide mimetics, and anti-Id mAbs. The results reveal isotype-related differences in fine specificities and Id for two mAb isotype switched families, thus establishing the validity of this observation with sets of homologous Abs. The results suggest that the C region affects V region protein conformation, leading to differences in fine specificity and Id. The finding that isotype can affect fine specificity has major implications for current concepts of the generation of secondary responses, idiotypic network regulation, and isotype function. Given that isotype class switching and Ig gene somatic hypermutation share molecular mechanisms, these observations unify these processes in the sense that both can alter specificity and affinity.

Original languageEnglish (US)
Pages (from-to)2132-2142
Number of pages11
JournalJournal of Immunology
Volume174
Issue number4
StatePublished - Feb 15 2005

Fingerprint

Immunoglobulin Class Switching
Immunoglobulin Somatic Hypermutation
Antibodies
Immunoglobulin Genes
Protein Conformation
Cryptococcus neoformans
Immunoglobulin G
Peptides
glucuronoxylomannan

ASJC Scopus subject areas

  • Immunology

Cite this

Variable-region-identical antibodies differing in isotype demonstrate differences in fine specificity and idiotype. / Torres, Marcela; May, Rena; Scharff, Matthew D.; Casadevall, Arturo.

In: Journal of Immunology, Vol. 174, No. 4, 15.02.2005, p. 2132-2142.

Research output: Contribution to journalArticle

@article{b7e5d845d2924bf2a4fe7f8045bc78ee,
title = "Variable-region-identical antibodies differing in isotype demonstrate differences in fine specificity and idiotype",
abstract = "A central tenet of the current understanding of the relationship between Ab structure and function is that the variable region domain is solely responsible for Ag specificity. However, this view was recently challenged by the observation that families of mouse-human chimeric Abs with identical V regions demonstrate differences in fine specificity and by reports of changes in Ab Id structure with isotype switching. Here we revisited this question by evaluating the reactivity of two families of murine IgG switch variants that differed in V region usage for Cryptococcus neoformans glucuronoxylomannan, glucuronoxylomannan peptide mimetics, and anti-Id mAbs. The results reveal isotype-related differences in fine specificities and Id for two mAb isotype switched families, thus establishing the validity of this observation with sets of homologous Abs. The results suggest that the C region affects V region protein conformation, leading to differences in fine specificity and Id. The finding that isotype can affect fine specificity has major implications for current concepts of the generation of secondary responses, idiotypic network regulation, and isotype function. Given that isotype class switching and Ig gene somatic hypermutation share molecular mechanisms, these observations unify these processes in the sense that both can alter specificity and affinity.",
author = "Marcela Torres and Rena May and Scharff, {Matthew D.} and Arturo Casadevall",
year = "2005",
month = "2",
day = "15",
language = "English (US)",
volume = "174",
pages = "2132--2142",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "4",

}

TY - JOUR

T1 - Variable-region-identical antibodies differing in isotype demonstrate differences in fine specificity and idiotype

AU - Torres, Marcela

AU - May, Rena

AU - Scharff, Matthew D.

AU - Casadevall, Arturo

PY - 2005/2/15

Y1 - 2005/2/15

N2 - A central tenet of the current understanding of the relationship between Ab structure and function is that the variable region domain is solely responsible for Ag specificity. However, this view was recently challenged by the observation that families of mouse-human chimeric Abs with identical V regions demonstrate differences in fine specificity and by reports of changes in Ab Id structure with isotype switching. Here we revisited this question by evaluating the reactivity of two families of murine IgG switch variants that differed in V region usage for Cryptococcus neoformans glucuronoxylomannan, glucuronoxylomannan peptide mimetics, and anti-Id mAbs. The results reveal isotype-related differences in fine specificities and Id for two mAb isotype switched families, thus establishing the validity of this observation with sets of homologous Abs. The results suggest that the C region affects V region protein conformation, leading to differences in fine specificity and Id. The finding that isotype can affect fine specificity has major implications for current concepts of the generation of secondary responses, idiotypic network regulation, and isotype function. Given that isotype class switching and Ig gene somatic hypermutation share molecular mechanisms, these observations unify these processes in the sense that both can alter specificity and affinity.

AB - A central tenet of the current understanding of the relationship between Ab structure and function is that the variable region domain is solely responsible for Ag specificity. However, this view was recently challenged by the observation that families of mouse-human chimeric Abs with identical V regions demonstrate differences in fine specificity and by reports of changes in Ab Id structure with isotype switching. Here we revisited this question by evaluating the reactivity of two families of murine IgG switch variants that differed in V region usage for Cryptococcus neoformans glucuronoxylomannan, glucuronoxylomannan peptide mimetics, and anti-Id mAbs. The results reveal isotype-related differences in fine specificities and Id for two mAb isotype switched families, thus establishing the validity of this observation with sets of homologous Abs. The results suggest that the C region affects V region protein conformation, leading to differences in fine specificity and Id. The finding that isotype can affect fine specificity has major implications for current concepts of the generation of secondary responses, idiotypic network regulation, and isotype function. Given that isotype class switching and Ig gene somatic hypermutation share molecular mechanisms, these observations unify these processes in the sense that both can alter specificity and affinity.

UR - http://www.scopus.com/inward/record.url?scp=13544277164&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=13544277164&partnerID=8YFLogxK

M3 - Article

C2 - 15699144

AN - SCOPUS:13544277164

VL - 174

SP - 2132

EP - 2142

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 4

ER -