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HIV gag protein is efficiently cross-presented when targeted with an antibody towards the DEC-205 receptor in Flt3 ligand-mobilized murine DC.

 Leonia Bozzacco  ;  Christine Trumpfheller  ;  Yaoxing Huang  ;  Maria Paula Longhi  ;  Irina Shimeliovich  ;  Joseph D. Schauer  ;  Chae Gyu Park  ;  Ralph M. Steinman 
 EUROPEAN JOURNAL OF IMMUNOLOGY, Vol.40(1) : 36-46, 2010 
Journal Title
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Animals ; Antibodies/immunology* ; Antigens, CD/immunology* ; CD8-Positive T-Lymphocytes/immunology ; Cell Line ; Cricetinae ; Cross Reactions ; Dendritic Cells/immunology* ; HIV/immunology* ; Lectins, C-Type/immunology* ; Membrane Proteins/immunology* ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Minor Histocompatibility Antigens ; Receptors, Cell Surface/immunology* ; gag Gene Products, Human Immunodeficiency Virus/immunology*
DC present exogenous proteins to MHC class I-restricted CD8+ T cells. This function does not require endogenous antigen synthesis within DC, providing the potential to elicit CD8+ T-cell responses to immune complexes, inactivated microbes, dying cells, and proteins such as OVA. In mice, the CD8+ or DEC-205+ DC are specialized for cross-presentation, and this subset can be increased 10-fold in numbers following Fms-like tyrosine kinase 3 ligand (Flt3L) treatment in vivo. Therefore, we studied cross-presentation by abundant Flt3L DC using HIV gag protein. When enriched by positive selection with anti-CD11c beads, cells from Flt3L mice are not only more abundant but are also more highly enriched in CD11chigh DC, particularly the DEC-205+ subset. DC cross-present HIV gag to primed CD8+ T cells, but when the antigen is delivered within an antibody to DEC-205 receptor, cross-presentation becomes 100-fold more efficient than non-targeted antigen. This finding requires gag to be engineered into anti-DEC antibody, not just mixed with antibody. Flt3L DC are a valuable tool to study cross-presentation, since their use overcomes the obstacle posed by the low number of cross-presenting DC in the steady state. These findings support future experiments to use Flt3L to enhance presentation of DC-targeted vaccines.
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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
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