Efficient delivery of T cell epitopes to APC by use of MHC class II-specific Troybodies.
A major objective in vaccine development is the design of reagents that give strong, specific T cell responses. We have constructed a series of rAb with specificity for MHC class II (I-E). Each has one of four different class II-restricted T cell epitopes genetically introduced into the first C domain of the H chain. These four epitopes are: 91-101 lambda2(315), which is presented by I-E(d); 110-120 hemagglutinin (I-E(d)); 323-339 OVA (I-A(d)); and 46-61 hen egg lysozyme (I-A(k)). We denote such APC-specific, epitope-containing Ab "Troybodies." When mixed with APC, all four class II-specific Troybodies were approximately 1,000 times more efficient at inducing specific T cell activation in vitro compared with nontargeting peptide Ab. Furthermore, they were 1,000-10,000 times more efficient than synthetic peptide or native protein. Conventional intracellular processing of the Troybodies was required to load the epitopes onto MHC class II. Different types of professional APC, such as purified B cells, dendritic cells, and macrophages, were equally efficient at processing and presenting the Troybodies. In vivo, class II-specific Troybodies were at least 100 times more efficient at targeting APC and activating TCR-transgenic T cells than were the nontargeting peptide Ab. Furthermore, they were 100-100,000 times more efficient than synthetic peptide or native protein. The study shows that class II-specific Troybodies can deliver a variety of T cell epitopes to professional APC for efficient presentation, in vitro as well as in vivo. Thus, Troybodies may be useful as tools in vaccine development.
Lunde
Elin
E
Institute of Immunology, University of Oslo, National Hospital, P.O. Box 1050 Blindern, N-0316 Oslo, Norway. elunde@bio.uio.no
Western
Karoline H
KH
Rasmussen
Ingunn B
IB
Sandlie
Inger
I
Bogen
Bjarne
B
D000818:Animals; D000911:Antibodies, Monoclonal / Q000235:genetics / Q000276:immunology*; D017951:Antigen Presentation; D000938:Antigen-Presenting Cells / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002460:Cell Line; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics; D003713:Dendritic Cells / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology*; D019672:Genes, T-Cell Receptor; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D008213:Lymphocyte Activation; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011993:Recombinant Fusion Proteins / Q000378:metabolism
D000911:Antibodies, Monoclonal; D004268:DNA-Binding Proteins; D018984:Epitopes, T-Lymphocyte; D000949:Histocompatibility Antigens Class II; C499308:Rag2 protein, mouse; D011993:Recombinant Fusion Proteins; C064655:V(D)J recombination activating protein 2