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.
Starnbach
Michael N
MN
Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, MA 02115, USA. starnbach@harvard.hms.edu
Loomis
Wendy P
WP
Ovendale
Pam
P
Regan
David
D
Hess
Bruce
B
Alderson
Mark R
MR
Fling
Steven P
SP
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