Chlamydia trachomatis (=C.t.) causes more than four million cases of sexually transmitted disease annually in the United States. Antibiotic treatment has not significantly reduced dissemination of C.t. and manipulation of the immune system with vaccines or other means may prove to be the best way of reducing case load and pathogenesis. Toward this end, the broad goal of the proposed work is to isolate and characterize T cell lines and clones from C.t-infected humans. The initial outgrowth of such T cells from peripheral blood will be stimulated with C.t. elementary bodies (=EBs) or lysates thereof and with purified MOMP, an immunodominant major outer membrane protein. The antigens will be presented by either autologous peripheral blood antigen-presenting cells (=APC) or by permanent cell lines derived form macrophages, endometrial- epithelial or B cells. Attempts will be made to detect antigen processing in exogenous and endogenous pathways. C.t.-response T cell clones will be derived early and characterized with regard to functional type and the HLA molecule each clone recognizes in association with a C.t. epitope. MOMP epitopes that are presented with specific HLA molecules will be identified by testing responsiveness of T cell clones to a collection of 25 amino acid-long synthetic peptides that have overlapping sequences spanning the MOMP sequence and that are presented by B cell APC lines that uniquely express the HLA molecule being tested. A search for non-MOMP antigens will be made by resolving total EB proteins by gel electrophoresis and isolating T cell lines or clones that respond to specific protein fractions. These T cells will also be characterized with regard to functional type and HLA specificity. Further protein fractionations will be used to identify the specific C.t. antigens using the characterized T cell clones as reagents.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program Projects (P01)
Project #
3P01AI034617-05S1
Application #
6099679
Study Section
Project Start
1998-09-01
Project End
2000-12-31
Budget Start
1997-10-01
Budget End
1998-09-30
Support Year
5
Fiscal Year
1998
Total Cost
Indirect Cost
Name
University of Wisconsin Madison
Department
Type
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715
Kalayoglu, Murat V; Libby, Peter; Byrne, Gerald I (2002) Chlamydia pneumoniae as an emerging risk factor in cardiovascular disease. JAMA 288:2724-31
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Kim, S K; DeMars, R (2001) Epitope clusters in the major outer membrane protein of Chlamydia trachomatis. Curr Opin Immunol 13:429-36
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Ortiz, L; Angevine, M; Kim, S K et al. (2000) T-cell epitopes in variable segments of Chlamydia trachomatis major outer membrane protein elicit serovar-specific immune responses in infected humans. Infect Immun 68:1719-23
LaVerda, D; Kalayoglu, M V; Byrne, G I (1999) Chlamydial heat shock proteins and disease pathology: new paradigms for old problems? Infect Dis Obstet Gynecol 7:64-71
Kim, S K; Angevine, M; Demick, K et al. (1999) Induction of HLA class I-restricted CD8+ CTLs specific for the major outer membrane protein of Chlamydia trachomatis in human genital tract infections. J Immunol 162:6855-66
Kane, C D; Vena, R M; Ouellette, S P et al. (1999) Intracellular tryptophan pool sizes may account for differences in gamma interferon-mediated inhibition and persistence of chlamydial growth in polarized and nonpolarized cells. Infect Immun 67:1666-71
Kalayoglu, M V; Byrne, G I (1998) A Chlamydia pneumoniae component that induces macrophage foam cell formation is chlamydial lipopolysaccharide. Infect Immun 66:5067-72
Kalayoglu, M V; Byrne, G I (1998) Induction of macrophage foam cell formation by Chlamydia pneumoniae. J Infect Dis 177:725-9

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