IL-32-Derived Dendritic Cells Cross-Present Defined Mycobacterium leprae Antigens to CD8+ T Cell | Posted on:2019-06-29 | Degree:M.S | Type:Thesis | University:University of California, Los Angeles | Candidate:Choi, Aaron Wonho | Full Text:PDF | GTID:2474390017987853 | Subject:Immunology | Abstract/Summary: | | Leprosy is a human disease caused by the intracellular pathogen Mycobacterium leprae. By investigating leprosy, we discovered a novel pathway involving NOD2-mediated induction of interleukin-32 (IL-32) triggering the differentiation of M. leprae infected monocytes into CD1+ dendritic cells (DCs) with professional antigen presenting cell function. These IL-32-derived DCs were able to "cross-present" antigen, that is capture exogenous antigen via the endocytic pathway and then present processed peptides via MHC class I to CD8+ T cells. It was also discovered that key components of the NOD2->IL-32->CD1+ DC pathway were highly expressed only in lesions of leprosy patients with cell-mediated immunity. We hypothesized that cross-presentation of M. leprae antigens by IL-32-derived DCs resulted in the activation of MHC class I-restricted CD8+ T cells. To test our hypothesis, we established CD8+ T cell clones from leprosy patients to putatively secreted M. leprae antigens. IL-32-derived DCs were able to cross-present exogenous recombinant M. leprae protein as well as live M. leprae to the CD8+ T cell clones. We conclude that IL-32-induced cross-presentation may play a role in CD8+ T cell responses in leprosy. | Keywords/Search Tags: | Cell, Leprae, Cd8, Cross-present, Leprosy, Il-32-derived | | Related items |
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