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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Huang, Yaoxing Trumpfheller, Christine Clausen, Björn E. Park, Chae Gyu Rodriguez, Anthony Fiorese, Christopher Lahoud, Mireille H. Lubkin, Ashira Steinman, Ralph M. Caminschi, Irina Idoyaga, Juliana |
| Description | Author Affiliation: Idoyaga J ( Laboratory of Cellular Physiology and Immunology and The Chris Browne Center for Immunology and Immune Diseases, The Rockefeller University, New York, NY 10065, USA.); |
| Abstract | Improved protein-based vaccines should facilitate the goal of effective vaccines against HIV and other pathogens. With respect to T cells, the efficiency of immunization, or 'immunogenicity,' is improved by targeting vaccine proteins to maturing dendritic cells (DCs) within mAbs to DC receptors. Here, we compared the capacity of Langerin/CD207, DEC205/CD205, and Clec9A receptors, each expressed on the CD8(+) DC subset in mice, to bring about immunization of microbial-specific T cells from the polyclonal repertoire, using HIV gag-p24 protein as an antigen. -Langerin mAb targeted splenic CD8(+) DCs selectively in vivo, whereas -DEC205 and -Clec9A mAbs targeted additional cell types. When the mAb heavy chains were engineered to express gag-p24, the -Langerin, -DEC205, and -Clec9A fusion mAbs given along with a maturation stimulus induced comparable levels of gag-specific T helper 1 (Th1) and CD8(+) T cells in BALB/c × C57BL/6 F1 mice. These immune T cells were more numerous than targeting the CD8(-) DC subset with -DCIR2-gag-p24. In an in vivo assay in which gag-primed T cells were used to report the early stages of T-cell responses, -Langerin, -DEC205, and -Clec9A also mediated cross-presentation to primed CD8(+) T cells if, in parallel to antigen uptake, the DCs were stimulated with -CD40. -Langerin, -DEC205, and -Clec9A targeting greatly enhanced T-cell immunization relative to nonbinding control mAb or nontargeted HIV gag-p24 protein. Therefore, when the appropriate subset of DCs is targeted with a vaccine protein, several different receptors expressed by that subset are able to initiate combined Th1 and CD8(+) immunity. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 6 |
| Volume Number | 108 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2011-02-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | AIDS Vaccines Immunology Antibodies, Monoclonal Pharmacology Antigens, CD8 Antigens, CD Antigens, Surface CD8-Positive T-Lymphocytes Dendritic Cells HIV Core Protein P24 Lectins, C-Type Mannose-Binding Lectins Receptors, Cell Surface Receptors, Immunologic Th1 Cells Animals Immunity, Cellular Drug Effects Mice Mice, Inbred BALB C Mice, Knockout Minor Histocompatibility Antigens Comparative Study Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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