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International Immunology Advance Access published online on February 4, 2008
International Immunology, doi:10.1093/intimm/dxm141
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© The Japanese Society for Immunology. 2008. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Recombinant antibodies for delivery of antigen: a single loop between β-strands in the constant region can accommodate long, complex and tandem T cell epitopes

Gro Tunheim1, Karoline W. Schjetne1, Ingunn B. Rasmussen2, Ludvig M. Sollid1, Inger Sandlie2 and Bjarne Bogen1

1 Center for Immune Regulation, Institute of Immunology, Medical Faculty, University of Oslo and Rikshospitalet University Hospital, Norway
2 Department of Molecular Biosciences, University of Oslo, Oslo, Norway

Correspondence to: Correspondence to: B. Bogen; E-mail: bjarne.bogen{at}medisin.uio.no

Recombinant antibodies are increasingly used for efficient delivery of T cell epitopes to antigen-presenting cells (APCs), both for vaccination purposes and for immune modulation. We have previously shown that recombinant antibodies can accommodate single T cell epitopes inserted into loops between β-strands in constant (C) domains. Such recombinant antibodies have in addition been equipped with variable regions that target APCs for increased delivery of C region T cell epitopes. We here show that loop 6 (loop FG) in CH1 of human {gamma}3 can be exchanged with (i) long T cell epitopes up to 37 amino acids, (ii) epitopes with complex secondary structure such as gluten epitopes with a type II polyproline helical confirmation and (iii) two tandemly linked T cell epitopes. T cell responses increased with T cell epitope elongation, presumably due to a positive influence of flanking residues. Recombinant antibodies targeted to either CD14 on monocytes or HLA-DP on monocytes and dendritic cells gave similar results and were 2–4 logs more efficient at stimulating human T cells than were non-targeted controls. Thus, single loops in C regions of recombinant antibodies seem versatile and may be used for delivery of lengthy, complex and multiple T cell epitopes to human APCs.

Keywords: autoimmunity, dendritic cells, human, monocytes/macrophages, vaccination

Transmitting editor: K. Inaba

Received 25 April 2006, accepted 6 December 2007.


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