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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
by
Huang, Yaoxing
, Lahoud, Mireille H
, Trumpfheller, Christine
, Steinman, Ralph M
, Park, Chae Gyu
, Rodriguez, Anthony
, Fiorese, Christopher
, Lubkin, Ashira
, Clausen, Björn E
, Caminschi, Irina
, Idoyaga, Juliana
in
AIDS Vaccines - immunology
/ AIDS Vaccines - pharmacology
/ Animals
/ antibodies
/ Antibodies, Monoclonal - immunology
/ Antibodies, Monoclonal - pharmacology
/ Antigen presentation
/ Antigens
/ Antigens, CD - immunology
/ Antigens, Surface - immunology
/ Biological Sciences
/ CD4-positive T-lymphocytes
/ CD8 antigen
/ CD8 Antigens
/ CD8-positive T-lymphocytes
/ CD8-Positive T-Lymphocytes - immunology
/ Combined vaccines
/ Cross priming
/ Dendritic cells
/ Dendritic Cells - immunology
/ Gag protein
/ Helper cells
/ HIV
/ HIV Core Protein p24 - immunology
/ HIV Core Protein p24 - pharmacology
/ Human immunodeficiency virus
/ immune response
/ Immune system
/ Immunity
/ Immunity, Cellular - drug effects
/ Immunity, Cellular - immunology
/ Immunization
/ Immunogenicity
/ Lectins
/ Lectins, C-Type - immunology
/ Lymphocytes T
/ Mannose-Binding Lectins - immunology
/ Maturation
/ Mice
/ Mice, Inbred BALB C
/ Mice, Knockout
/ Minor Histocompatibility Antigens
/ Monoclonal antibodies
/ Pathogens
/ Proteins
/ Receptors
/ Receptors, Cell Surface - immunology
/ Receptors, Immunologic - immunology
/ Rodents
/ Spleen
/ T cell receptors
/ T lymphocytes
/ Th1 Cells - immunology
/ Vaccination
/ Vaccines
2011
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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
by
Huang, Yaoxing
, Lahoud, Mireille H
, Trumpfheller, Christine
, Steinman, Ralph M
, Park, Chae Gyu
, Rodriguez, Anthony
, Fiorese, Christopher
, Lubkin, Ashira
, Clausen, Björn E
, Caminschi, Irina
, Idoyaga, Juliana
in
AIDS Vaccines - immunology
/ AIDS Vaccines - pharmacology
/ Animals
/ antibodies
/ Antibodies, Monoclonal - immunology
/ Antibodies, Monoclonal - pharmacology
/ Antigen presentation
/ Antigens
/ Antigens, CD - immunology
/ Antigens, Surface - immunology
/ Biological Sciences
/ CD4-positive T-lymphocytes
/ CD8 antigen
/ CD8 Antigens
/ CD8-positive T-lymphocytes
/ CD8-Positive T-Lymphocytes - immunology
/ Combined vaccines
/ Cross priming
/ Dendritic cells
/ Dendritic Cells - immunology
/ Gag protein
/ Helper cells
/ HIV
/ HIV Core Protein p24 - immunology
/ HIV Core Protein p24 - pharmacology
/ Human immunodeficiency virus
/ immune response
/ Immune system
/ Immunity
/ Immunity, Cellular - drug effects
/ Immunity, Cellular - immunology
/ Immunization
/ Immunogenicity
/ Lectins
/ Lectins, C-Type - immunology
/ Lymphocytes T
/ Mannose-Binding Lectins - immunology
/ Maturation
/ Mice
/ Mice, Inbred BALB C
/ Mice, Knockout
/ Minor Histocompatibility Antigens
/ Monoclonal antibodies
/ Pathogens
/ Proteins
/ Receptors
/ Receptors, Cell Surface - immunology
/ Receptors, Immunologic - immunology
/ Rodents
/ Spleen
/ T cell receptors
/ T lymphocytes
/ Th1 Cells - immunology
/ Vaccination
/ Vaccines
2011
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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
by
Huang, Yaoxing
, Lahoud, Mireille H
, Trumpfheller, Christine
, Steinman, Ralph M
, Park, Chae Gyu
, Rodriguez, Anthony
, Fiorese, Christopher
, Lubkin, Ashira
, Clausen, Björn E
, Caminschi, Irina
, Idoyaga, Juliana
in
AIDS Vaccines - immunology
/ AIDS Vaccines - pharmacology
/ Animals
/ antibodies
/ Antibodies, Monoclonal - immunology
/ Antibodies, Monoclonal - pharmacology
/ Antigen presentation
/ Antigens
/ Antigens, CD - immunology
/ Antigens, Surface - immunology
/ Biological Sciences
/ CD4-positive T-lymphocytes
/ CD8 antigen
/ CD8 Antigens
/ CD8-positive T-lymphocytes
/ CD8-Positive T-Lymphocytes - immunology
/ Combined vaccines
/ Cross priming
/ Dendritic cells
/ Dendritic Cells - immunology
/ Gag protein
/ Helper cells
/ HIV
/ HIV Core Protein p24 - immunology
/ HIV Core Protein p24 - pharmacology
/ Human immunodeficiency virus
/ immune response
/ Immune system
/ Immunity
/ Immunity, Cellular - drug effects
/ Immunity, Cellular - immunology
/ Immunization
/ Immunogenicity
/ Lectins
/ Lectins, C-Type - immunology
/ Lymphocytes T
/ Mannose-Binding Lectins - immunology
/ Maturation
/ Mice
/ Mice, Inbred BALB C
/ Mice, Knockout
/ Minor Histocompatibility Antigens
/ Monoclonal antibodies
/ Pathogens
/ Proteins
/ Receptors
/ Receptors, Cell Surface - immunology
/ Receptors, Immunologic - immunology
/ Rodents
/ Spleen
/ T cell receptors
/ T lymphocytes
/ Th1 Cells - immunology
/ Vaccination
/ Vaccines
2011
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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
Journal Article
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
2011
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Overview
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 x 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.
Publisher
National Academy of Sciences,National Acad Sciences
Subject
/ AIDS Vaccines - pharmacology
/ Animals
/ Antibodies, Monoclonal - immunology
/ Antibodies, Monoclonal - pharmacology
/ Antigens
/ Antigens, Surface - immunology
/ CD8-Positive T-Lymphocytes - immunology
/ Dendritic Cells - immunology
/ HIV
/ HIV Core Protein p24 - immunology
/ HIV Core Protein p24 - pharmacology
/ Human immunodeficiency virus
/ Immunity
/ Immunity, Cellular - drug effects
/ Immunity, Cellular - immunology
/ Lectins
/ Lectins, C-Type - immunology
/ Mannose-Binding Lectins - immunology
/ Mice
/ Minor Histocompatibility Antigens
/ Proteins
/ Receptors, Cell Surface - immunology
/ Receptors, Immunologic - immunology
/ Rodents
/ Spleen
/ Vaccines
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