Discovery of CD8 + T cell epitopes in Chlamydia trachomatis infection through use of caged class I MHC tetramers
| Autor: | Jia-huai Wang, Rob Meijers, George W. Bell, Gijsbert M. Grotenbreg, Hidde L. Ploegh, Nadia R. Roan, Eduardo Guillen, Michael N. Starnbach |
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| Rok vydání: | 2008 |
| Předmět: |
Models
Molecular Light T cell Molecular Sequence Data Epitopes T-Lymphocyte chemical and pharmacologic phenomena Chlamydia trachomatis CD8-Positive T-Lymphocytes Crystallography X-Ray Ligands Major histocompatibility complex Epitope Mice MHC class I medicine Animals Cytotoxic T cell Amino Acid Sequence Protein Structure Quaternary Peptide sequence Multidisciplinary biology Histocompatibility Antigens Class I H-2 Antigens Computational Biology Reproducibility of Results Stereoisomerism Chlamydia Infections Biological Sciences MHC restriction Molecular biology Cell biology Mice Inbred C57BL medicine.anatomical_structure Solubility biology.protein Peptides CD8 |
| Zdroj: | Proceedings of the National Academy of Sciences. 105:3831-3836 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.0711504105 |
| Popis: | Class I MHC tetramers allow direct phenotypic identification of CD8 + T cell populations, but their production remains laborious. A peptide exchange strategy that employs class I MHC products loaded with conditional ligands (caged MHC molecules) provides a fast and straightforward method to obtain diverse arrays of class I MHC tetramers and facilitates CD8 + T cell epitope discovery. Here, we describe the development of photocleavable analogs of the FAPGNYPAL (SV9) epitope that bind H-2K b and H-2D b with full retention of their structural and functional integrity. We ranked all possible H-2K b octameric and H-2D b nonameric epitopes that span the genome of Chlamydia trachomatis and prepared MHC tetramers from ≈2,000 of the highest scoring peptides by replacement of the SV9 analog with the peptide of choice. The resulting 2,000-member class I MHC tetramer array allowed the discovery of two variants of an epitope derived from polymorphic membrane protein I (PmpI) and an assessment of the kinetics of emergence and the effector function of the corresponding CD8 + T cells. |
| Databáze: | OpenAIRE |
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