       Document 0474
 DOCN  M9610474
 TI    Cell-invasive activity of epitope-tagged adenylate cyclase of Bordetella
       pertussis allows in vitro presentation of a foreign epitope to CD8+
       cytotoxic T cells.
 DT    9601
 AU    Sebo P; Fayolle C; d'Andria O; Ladant D; Leclerc C; Ullmann A; Unite de
       Biochimie des Regulations Cellulaires, Institut; Pasteur, Paris, France.
 SO    Infect Immun. 1995 Oct;63(10):3851-7. Unique Identifier : AIDSLINE
       MED/96009738
 AB    The adenylate cyclase (AC) toxin (CyaA) of Bordetella pertussis has an
       invasive catalytic domain (AC domain) which penetrates the cytoplasmic
       membrane of a variety of eukaryotic cells and intoxicates them by
       unregulated synthesis of cyclic AMP. Previous work led to identification
       of five permissive sites in the AC domain at which heterologous peptides
       are accommodated without affecting its enzymatic properties. We have
       constructed a set of CyaA toxins tagged at these permissive sites by
       insertion of a CD8+ T-cell epitope, RPQASGVYMGNLTAQ, from the
       nucleoprotein of lymphocytic choriomeningitis virus. Introduction of the
       epitope at any of the five sites did not affect the capacity of the
       toxin to deliver its AC domain into target cells. Moreover, the toxin
       with the inserted epitope was shown to sensitize target cells for lysis
       by epitope-specific CD8+ cytotoxic T lymphocytes in vitro, showing that
       the tagged AC was processed for presentation of the lymphocytic
       choriomeningitis virus epitope in association with the major
       histocompatibility complex class I molecules. This finding indicates
       that by virtue of delivery of foreign epitopes into the
       antigen-presenting cells, purpose-designed recombinant CyaAs may be
       useful for induction of specific major histocompatibility complex class
       I-restricted cell-mediated immunity also in vivo.
 DE    Adenyl Cyclase/*TOXICITY  Amino Acid Sequence  Animal  *Antigen
       Presentation  Bacterial Toxins/*TOXICITY  Base Sequence  Bordetella
       pertussis/*PATHOGENICITY  CD8-Positive T-Lymphocytes/*IMMUNOLOGY
       *Epitopes  Female  Histocompatibility Antigens Class I/IMMUNOLOGY
       Lymphocytic Choriomeningitis Virus/IMMUNOLOGY  Mice  Mice, Inbred BALB C
       Molecular Sequence Data  Recombinant Proteins/TOXICITY  Sheep  Support,
       Non-U.S. Gov't  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

