Chlamydia trachomatis (Ct) is the most common cause of bacterial sexually transmitted disease worldwide. In the majority of infected individuals they are asymptomatic. This poses a heath risk for women, causing pelvic inflammation and tubal infertility, and for newborns from infected mothers. Our goal is to characterize the human T cell immune response to Ct in infected individuals with the goal of identifying immunogenic proteins and peptides that could be used for vaccine development. We will determine whether CD4 or CD8 T cell responses can be elicited against Ct proteins that enter the MHC class I or class II antigen processing pathway or are likely to enter those pathways. Specific peptide epitopes from these proteins and the HLA allotypes that present the peptides will be determined using a unique panel of B lymphoblastoid lines expressing single HLA antigens. Our hypothesis is that some regions of immunogenic proteins will contain epitope clusters for both CD4 and CD8 T cells as we found for the major outer membrane protein MOMP. The functional characteristics of the Ct-specific T cells will be determined using antibodies against cytokines, proteins involved in cytotoxicity, and cell surface molecules. Assays such as the Lysispot assay will be used to determine CTL function. Ct-specific T cells in the blood of infected individuals will be enumerated with MHC class I tetramer and class II tetramers. We will determine if the CD8 T cells recognizing Ct antigens are functional CTL cells or potentially """"""""exhausted"""""""" T cells lacking CTL activity, which has been found in chronic viral infections. The potential for immunogenic epitopes to cross-protect other Ct species such as C. pneumonia and C. psittaci will be determined by sequence comparisons. Characterizing human T cell responses to Ct is important for understanding immunity to Ct in humans and for future vaccine development.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI049571-05
Application #
7414396
Study Section
Special Emphasis Panel (ZRG1-BM-1 (01))
Program Officer
Hiltke, Thomas J
Project Start
2004-05-01
Project End
2010-04-30
Budget Start
2008-05-01
Budget End
2010-04-30
Support Year
5
Fiscal Year
2008
Total Cost
$342,186
Indirect Cost
Name
Yale University
Department
Pathology
Type
Schools of Medicine
DUNS #
043207562
City
New Haven
State
CT
Country
United States
Zip Code
06520
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Mulla, Melissa J; Myrtolli, Kledia; Potter, Julie et al. (2011) Uric acid induces trophoblast IL-1? production via the inflammasome: implications for the pathogenesis of preeclampsia. Am J Reprod Immunol 65:542-8
de la Torre, Eugenia; Mulla, Melissa J; Yu, Andrew G et al. (2009) Chlamydia trachomatis infection modulates trophoblast cytokine/chemokine production. J Immunol 182:3735-45
Leonhardt, Ralf M; Lee, Seung-Joon; Kavathas, Paula B et al. (2007) Severe tryptophan starvation blocks onset of conventional persistence and reduces reactivation of Chlamydia trachomatis. Infect Immun 75:5105-17