Can isotype switch modulate antigen-binding affinity and influence clonal selection?
Eur J Immunol
; 30(12): 3387-95, 2000 Dec.
Article
em En
| MEDLINE
| ID: mdl-11093156
ABSTRACT
Four different monoclonal Ig (MIg) (IgA1kappa, IgG1kappa, IgG2kappa and IgG4kappa) displaying anti-tubulin activity were detected in the serum from a lymphoma patient. The complete sequence of three of these MIg showed identical V(H) and V(L) domains and the presence of mutations compatible with an antigen-driven process. Surprisingly, despite complete homology in their variable domains, IgA1kappa, IgG1kappa, or their Fab fragments bound to a common motif recognized in beta tubulin, with significant differences in affinity (IgA1kappa 1.52x10(-8) M, and IgG1kappa 2.09x10(-7) M). To substantiate these results, the V(H) and V(L) domains from IgA1kappa were cloned and introduced into expression vectors containing the constant kappa exon and either the mu or the gamma1 constant exon, and complete recombinant IgMkappa and IgG1kappa were obtained. Like the IgA1kappa, the IgMkappa construction bound to the tubulin epitope with consistent affinity (7.7x10(-9) M), whereas the IgG1kappa construction displayed a significantly lower affinity (3.28x10(-7) M). These results provide definitive evidence that isotype can influence binding affinity to antigen and suggest that malignant transformation occurred at the germinal center once the mutational process was achieved and the switch process was still active.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Switching de Imunoglobulina
/
Reações Antígeno-Anticorpo
Limite:
Humans
Idioma:
En
Revista:
Eur J Immunol
Ano de publicação:
2000
Tipo de documento:
Article
País de afiliação:
França