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* Department of Microbiology and Molecular Genetics,
Harvard Medical School, Boston, MA 02115; and
Department of Immunology, Corixa
Corporation, Seattle, WA 98104
During its developmental cycle, the intracellular bacterial
pathogen Chlamydia trachomatis remains confined within a
protective vacuole known as an inclusion. Nevertheless,
CD8+ T cells that recognize Chlamydia Ags in the
context of MHC class I molecules are primed during infection. MHC
class I-restricted presentation of these Ags suggests that these
proteins or domains from them have access to the host cell cytoplasm.
Chlamydia products with access to the host cell cytoplasm
define a subset of molecules uniquely positioned to interface with
the intracellular environment during the pathogen’s developmental
cycle. In addition to their use as candidate Ags for stimulating
CD8+ T cells, these proteins represent novel candidates
for therapeutic intervention of infection. In this study, we use
C. trachomatis-specific murine T cells and an
expression-cloning strategy to show that CT442 from Chlamydia
is targeted by CD8+ T cells. CT442, also known as CrpA, is
a 15-kDa protein of undefined function that has previously been shown
to be associated with the Chlamydia inclusion membrane. We
show that: 1) CD8+ T cells specific for an
H-2Db-restricted epitope from CrpA are elicited at a significant
level (
4% of splenic
CD8+ T cells) in mice in response to infection; 2) the
response to this epitope correlates with clearance of the organism
from infected mice; and 3) immunization with recombinant vaccinia
virus expressing CrpA elicits partial protective immunity to
subsequent i.v. challenge with C. trachomatis.
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