Epitope-specific antibody and suppression of autoantibody responses against a hybrid self protein.
J Immunol
; 161(12): 6518-25, 1998 Dec 15.
Article
em En
| MEDLINE
| ID: mdl-9862676
ABSTRACT
This study addresses the relationship of epitope-specific Ab responses and alternative autoantibody responses in a model system in which an antigenized self protein serves as the carrier for a defined heterologous B cell epitope. Ubiquitin, a nonimmunogenic self protein, was engineered to present heterologous B and T cell epitopes in the recombinant molecule. Fusion to the C terminus introduced a universal T cell epitope from a Mycobacterium tuberculosis Ag. The B cell epitope was created by inserting a 12-residue loop sequence of HIV-1 gp120 at a surface-exposed position of ubiquitin. These modifications preserved the ubiquitin fold, allowing a new conformational epitope to be presented among native self epitopes. Mice immunized with the hybrid protein bearing only the mycobacterial T cell epitope elicited a strong autoantibody response to native ubiquitin. In contrast, antisera elicited against hybrid ubiquitin presenting the HIV B cell epitope reacted specifically with the foreign epitope but not with native ubiquitin. Absence of autoantibody in the response was attributed to poor competition of autoreactive B cells for limiting T cell help. Both types of responses were associated with Th responses to defined epitopes of the ubiquitin hybrid protein. These results may have implications for a tolerance mechanism dependent on B-T cell cooperation.
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Coleções:
01-internacional
Contexto em Saúde:
2_ODS3
Base de dados:
MEDLINE
Assunto principal:
Autoanticorpos
/
Proteínas Recombinantes de Fusão
/
Ubiquitinas
/
Proteína gp120 do Envelope de HIV
/
Anticorpos Antibacterianos
/
Epitopos
/
Antígenos de Bactérias
Limite:
Animals
Idioma:
En
Revista:
J Immunol
Ano de publicação:
1998
Tipo de documento:
Article