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Comparable T helper 1 (Th1) and CD8 T-cell immunity by targeting HIV gag p24 to CD8 dendritic cells within antibodies to Langerin, DEC205, and Clec9A


Idoyaga, J; Lubkin, A; Fiorese, C; Lahoud, MH; Caminschi, I; Huang, YX; Rodriguez, A; Clausen, BE; Park, CG; Trumpfheller, C; Steinman, RM
2011-02-08
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Journal Article
108
6
2384-2389
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. alpha-Langerin mAb targeted splenic CD8(+) DCs selectively in vivo, whereas alpha-DEC205 and alpha-Clec9A mAbs targeted additional cell types. When the mAb heavy chains were engineered to express gag-p24, the alpha-Langerin, alpha-DEC205, and alpha-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 x C57BL/6 F1 mice. These immune T cells were more numerous than targeting the CD8(-) DC subset with alpha-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, alpha-Langerin, alpha-DEC205, and alpha-Clec9A also mediated cross-presentation to primed CD8(+) T cells if, in parallel to antigen uptake, the DCs were stimulated with alpha-CD40. alpha-Langerin, alpha-DEC205, and alpha-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.
NATL ACAD SCIENCES
C-TYPE LECTIN; SUBSETS IN-VIVO; MONOCLONAL-ANTIBODY; DEC-205 RECEPTOR; STEADY-STATE; ANTIGEN PRESENTATION; CROSS-PRESENTATION; CUTTING EDGE; DYING CELLS; IFN-GAMMA
10.1073/pnas.1019547108
Refer to copyright notice on published article.

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Creation Date 2011-02-08 12:00:00