An inclusion membrane protein from Chlamydia trachomatis enters the MHC class I pathway and stimulates a CD8+ T cell response.
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-2D(b)-restricted epitope from CrpA are elicited at a significant level (approximately 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.
Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, MA 02115, USA. starnbach@harvard.hms.edu
Michael N
MN
Starnbach
Wendy P
WP
Loomis
Pam
P
Ovendale
David
D
Regan
Bruce
B
Hess
Mark R
MR
Alderson
Steven P
SP
Fling
D000595:Amino Acid Sequence; D000818:Animals; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology*; D002460:Cell Line; D002690:Chlamydia Infections / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control; D002692:Chlamydia trachomatis / Q000235:genetics / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D006183:H-2 Antigens / Q000276:immunology* / Q000378:metabolism; D006367:HeLa Cells; D064532:Histocompatibility Antigen H-2D; D006801:Humans; D002479:Inclusion Bodies / Q000276:immunology* / Q000382:microbiology; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D014162:Transfection; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology; D014615:Vaccinia / Q000235:genetics / Q000276:immunology
D001425:Bacterial Outer Membrane Proteins; D018984:Epitopes, T-Lymphocyte; D006183:H-2 Antigens; D064532:Histocompatibility Antigen H-2D; C063931:Omp2 protein, bacteria; D014614:Vaccines, Synthetic