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1996-01-30
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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).