Highly efficient antigen targeting to M-DC8+ dendritic cells via FcgammaRIII/CD16-specific antibody conjugates.
Conjugates of peptide antigens with antibodies specifically recognizing surface molecules on dendritic cells (DC) represent an attractive approach to target antigens to antigen-presenting cells (APC) for the induction of specific T cell responses. The present study evaluates the potential of M-DC8(+) DC, a sub-population of professional APC in the blood, for an antibody-based vaccination strategy. We prepared, by chemical cross-linking, conjugates of peptide model antigens with antibodies directed against different cell surface molecules of DC. Antigen-peptide conjugates using an anti-CD16 (FcgammaRIII) antibody were most potent in inducing in vitro activation of a specific CD4(+) T cell response. They were at least 300 times more efficient than two other antibody-antigen conjugates and approximately 500 times more efficient than unconjugated antigen peptides. Our data demonstrate that specific antigen targeting via CD16 on M-DC8(+) DC is a promising vaccination approach for the efficient induction of specific CD4(+) T cell responses ex vivo, and perhaps in vivo.
Mende
Ines
I
Micromet AG, Staffelseestrasse 2, 81477 Munich, Germany.
Hoffmann
Patrick
P
Wolf
Andreas
A
Lutterbüse
Ralf
R
Kopp
Eugen
E
Baeuerle
Patrick A
PA
de Baey
Annegret
A
Kufer
Peter
P
D000906:Antibodies / Q000276:immunology; D017951:Antigen Presentation; D000941:Antigens / Q000276:immunology; D015703:Antigens, CD / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D045142:Cross-Priming; D003713:Dendritic Cells / Q000145:classification / Q000166:cytology / Q000276:immunology*; D006801:Humans; D018796:Immunoconjugates / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000166:cytology; D008213:Lymphocyte Activation; D017452:Receptors, IgG / Q000276:immunology*; D013744:Tetanus Toxin / Q000276:immunology; D014612:Vaccines
D000906:Antibodies; D000941:Antigens; D015703:Antigens, CD; D018796:Immunoconjugates; D017452:Receptors, IgG; D013744:Tetanus Toxin; D014612:Vaccines