Epitope-specific antibody and suppression of autoantibody responses against a hybrid self protein

Gerald L. Lohnas, Steven F. Roberts, Aprile Pilon, Alfonso Tramontano

Research output: Contribution to journalArticle

10 Scopus citations

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 HFV-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.

Original languageEnglish (US)
Pages (from-to)6518-6525
Number of pages8
JournalJournal of Immunology
Volume161
Issue number12
StatePublished - Dec 15 1998
Externally publishedYes

ASJC Scopus subject areas

  • Immunology

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    Lohnas, G. L., Roberts, S. F., Pilon, A., & Tramontano, A. (1998). Epitope-specific antibody and suppression of autoantibody responses against a hybrid self protein. Journal of Immunology, 161(12), 6518-6525.