'Troy-bodies': antibodies as vector proteins for T cell epitopes.
A major objective in vaccine development is the design of reagents that give a strong, specific T cell response. Targeting of antigens to antigen presenting cells (APC) results in enhanced antigen presentation and T cell activation. In this paper, we describe a novel targeting reagent denoted 'Troy-bodies', namely recombinant antibodies with APC-specificity and with T cell epitopes integrated in their C regions. We have made such antibodies with V regions specific for either IgD or MHC class II, and five different T cell epitopes have been tested. All epitopes could be introduced into loops of C domains without disrupting immunoglobulin (Ig) folding. Four have been tested in T cell activation studies, and all could be released and presented by APC. Furthermore, whether IgD- or MHC-specific, the molecules tested enhanced T cell stimulation compared to non-specific control antibodies in vitro as well as in vivo. Using this technology, specific reagents can be designed that target selected antigenic peptides to an APC of choice. Troy-bodies may therefore be useful for manipulation of immune responses, and in particular for vaccination purposes.
Lunde
E
E
Institute of Immunology, The National Hospital, N-0027, Oslo, Norway.
Rasmussen
I B
IB
Eidem
J K
JK
Gregers
T F
TF
Western
K H
KH
Bogen
B
B
Sandlie
I
I
D000818:Animals; D000906:Antibodies / Q000235:genetics / Q000276:immunology*; D000918:Antibody Specificity; D000938:Antigen-Presenting Cells / Q000276:immunology*; D000939:Epitopes / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006801:Humans; D007072:Immunoglobulin D / Q000276:immunology; D007135:Immunoglobulin Variable Region / Q000737:chemistry; D066298:In Vitro Techniques; D051379:Mice; D008807:Mice, Inbred BALB C; D008961:Models, Structural; D016254:Mutagenesis, Insertional; D009592:Nitrohydroxyiodophenylacetate; D015202:Protein Engineering; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D000906:Antibodies; D000939:Epitopes; D000949:Histocompatibility Antigens Class II; D007072:Immunoglobulin D; D007135:Immunoglobulin Variable Region; D011994:Recombinant Proteins; D009592:Nitrohydroxyiodophenylacetate