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Chlamydia trachomatis major outer membrane protein (MOMP) epitopes that activate HLA class II-restricted T cells from
L Ortiz1, K P Demick, J W Petersen
1Department of Medical Microbiology and Immunology, University of Wisconsin Medical School, Madison 53706, USA.
Abstract:
We localized peptide epitopes within the Chlamydia trachomatis (Ct) major outer membrane protein (MOMP) that activate human T cells. T-MOMP' cells were prepared by culturing PBL from 38 humans who had Ct infections in the presence of Ct serovar E MOMP. Some epitopes were first localized by quantifying proliferative responses of T-MOMP' cells to overlapping MOMP segments (sixths) that were produced in Escherichia coli. Further localization was achieved by using overlapping synthetic 16-22 mers that spanned stimulatory MOMP sixths as Ags. The APCs used were human B cell lines (LCL) that were matched or mismatched with respect to HLA class II alleles of the T-MOMP' cells. T cell epitopes were detected in 18 Ct serovar E MOMP 16-22 mers and were presented in association with HLA-DR1, -7, -13, -17, HLA-DRw52, HLA-DQ3 and at least two from among HLA-DR4, -8, -11, -14, -18, in probable addition to HLA-DP4. Peptide 249-265 stimulated T-MOMP' cells from 83% of the subjects; studies with overlapping 11-13 mers spanning peptide 249-265 revealed at least six epitopes presented with different HLA-class II allotypes. Diverse T-MOMP' cultures responded to between 2 and 7 MOMP epitopes. All but 1 of the 23 epitopes localized to date are distributed among four MOMP constant segments. T-MOMP' cells from subjects infected with serovars other than E also responded.
Insights
Researchers identified specific peptide fragments of Chlamydia trachomatis major outer membrane protein (MOMP) that trigger human T-cell responses. These T-cell epitopes are crucial for understanding Chlamydia trachomatis immunity.
Area of Science:
- Immunology
- Microbiology
- Molecular Biology
Background:
- Chlamydia trachomatis (Ct) is a significant human pathogen.
- The major outer membrane protein (MOMP) is a key target for immune responses.
- Understanding T-cell epitopes within MOMP is crucial for vaccine development and immunodiagnostics.
Purpose of the Study:
- To localize specific peptide epitopes within Ct MOMP that activate human T cells.
- To investigate the association of these epitopes with human leukocyte antigen (HLA) class II alleles.
- To characterize the breadth of T-cell responses to MOMP epitopes in individuals with Ct infections.
Main Methods:
- Culturing peripheral blood lymphocytes (PBL) from infected individuals with Ct MOMP.
- Quantifying T-cell proliferation in response to overlapping MOMP segments and synthetic peptides.
- Mapping epitopes using antigen-presenting cells (APCs) matched for HLA class II alleles.
Main Results:
- Identified 18 peptide epitopes within Ct serovar E MOMP recognized by human T cells.
- Detected epitopes presented by multiple HLA-DR, HLA-DQ, and potentially HLA-DP alleles.
- A specific peptide (249-265) stimulated T cells in 83% of subjects, with at least six sub-epitopes identified.
- Responses varied, with individuals recognizing 2-7 MOMP epitopes, primarily located in constant regions.
Conclusions:
- Ct MOMP contains multiple T-cell epitopes that are presented by diverse HLA class II molecules.
- These findings provide a basis for developing T-cell based diagnostics and vaccines against Chlamydia trachomatis.
- Immune responses to MOMP epitopes are observed across different Chlamydia serovars.