The immunoglobulin heavy chain constant region affects kinetic and thermodynamic parameters of antibody variable region interactions with antigen

Marcela Torres, Narcis Fernández-Fuentes, Andras Fiser, Arturo Casadevall

Research output: Contribution to journalArticle

76 Citations (Scopus)

Abstract

A central dogma in immunology is that antibody specificity is a function of the variable (V) region. However serological analysis of IgG1, IgG2a, and IgG2b switch variants of murine monoclonal antibody (mAb) 3E5 IgG3 with identical V domains revealed apparent specificity differences for Cryptococcus neoformans glucuronoxylomannan (GXM). Kinetic and thermodynamic binding properties of mAbs 3E5 to a 12-mer peptide mimetic of GXM revealed differences in the affinity of these mAbs for a monovalent ligand, a result that implied that the constant (C) region affects the secondary structure of the antigen binding site, thus accounting for variations in specificity. Structural models of mAbs 3E5 suggested that isotype-related differences in binding resulted from amino acid sequence polymorphisms in the C region. This study implies that isotype switching is another mechanism for generating diversity in antigen binding and that isotype restriction of certain antibody responses may reflect structural constraints imposed by C region on V region binding. Furthermore, isotype affected the polyreactivity of V region identical antibodies, implying a role for C region in determining self-reactivity.

Original languageEnglish (US)
Pages (from-to)13917-13927
Number of pages11
JournalJournal of Biological Chemistry
Volume282
Issue number18
DOIs
StatePublished - May 4 2007

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Immunoglobulin Heavy Chains
Thermodynamics
Immunoglobulin G
Immunoglobulin Class Switching
Antigens
Cryptococcus neoformans
Kinetics
Antibody Specificity
Antibodies
Structural Models
Allergy and Immunology
Immunology
Antibody Formation
Amino Acid Sequence
Binding Sites
Monoclonal Antibodies
Ligands
Polymorphism
Peptides
Switches

ASJC Scopus subject areas

  • Biochemistry

Cite this

The immunoglobulin heavy chain constant region affects kinetic and thermodynamic parameters of antibody variable region interactions with antigen. / Torres, Marcela; Fernández-Fuentes, Narcis; Fiser, Andras; Casadevall, Arturo.

In: Journal of Biological Chemistry, Vol. 282, No. 18, 04.05.2007, p. 13917-13927.

Research output: Contribution to journalArticle

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