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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.

Authors
 Juliana Idoyaga  ;  Ashira Lubkin  ;  Christopher Fiorese  ;  Mireille H. Lahoud  ;  Irina Caminschi  ;  Yaoxing Huang  ;  Anthony Rodriguez  ;  Björn E. Clausen  ;  Chae Gyu Park  ;  Christine Trumpfheller  ;  Ralph M. Steinman 
Citation
 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol.108(6) : 2384-2389, 2011 
Journal Title
 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 
ISSN
 0027-8424 
Issue Date
2011
MeSH
AIDS Vaccines/immunology* ; AIDS Vaccines/pharmacology ; Animals ; Antibodies, Monoclonal/immunology ; Antibodies, Monoclonal/pharmacology* ; Antigens, CD/immunology* ; Antigens, Surface/immunology* ; CD8 Antigens* ; CD8-Positive T-Lymphocytes/immunology* ; Dendritic Cells/immunology* ; HIV Core Protein p24/immunology* ; HIV Core Protein p24/pharmacology ; Immunity, Cellular/drug effects ; Immunity, Cellular/immunology ; Lectins, C-Type/immunology* ; Mannose-Binding Lectins/immunology* ; Mice ; Mice, Inbred BALB C ; Mice, Knockout ; Minor Histocompatibility Antigens ; Receptors, Cell Surface/immunology* ; Receptors, Immunologic/immunology* ; Th1 Cells/immunology*
Keywords
antigen presentation ; C-type lectins ; cross-priming
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. α-Langerin mAb targeted splenic CD8(+) DCs selectively in vivo, whereas α-DEC205 and α-Clec9A mAbs targeted additional cell types. When the mAb heavy chains were engineered to express gag-p24, the α-Langerin, α-DEC205, and α-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 α-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, α-Langerin, α-DEC205, and α-Clec9A also mediated cross-presentation to primed CD8(+) T cells if, in parallel to antigen uptake, the DCs were stimulated with α-CD40. α-Langerin, α-DEC205, and α-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.
Files in This Item:
T201194237.pdf Download
DOI
10.1073/pnas.1019547108
Appears in Collections:
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
Yonsei Authors
Park, Chae Gyu(박채규) ORCID logo https://orcid.org/0000-0003-1906-1308
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/95413
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