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Published online before print December 2, 2004

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(Journal of Leukocyte Biology. 2005;77:303-310.)
© 2005 by Society for Leukocyte Biology

Human CD14 is an efficient target for recombinant immunoglobulin vaccine constructs that deliver T cell epitopes

Gro Tunheim^*,1, Karoline W. Schjetne^*, Agnete B. Fredriksen^*, Inger Sandlie and Bjarne Bogen^*

^* Institute of Immunology, University of Oslo and Rikshospitalet University Hospital, Norway; and
Department of Molecular Biosciences, University of Oslo, Norway

¹ Correspondence: Institute of Immunology, University of Oslo and Rikshospitalet University Hospital, N-0027 Oslo, Norway. E-mail: gro.tunheim{at}medisin.uio.no; bjarne.bogen{at}medisin.uio.no

It has been shown in the mouse that recombinant immunoglobulin (Ig) molecules with T cell epitopes inserted into the constant domain (Troybodies) can target antigen-presenting cells (APC) for efficient delivery of T cell epitopes. Here, we have extended the Troybody concept to human applications. Moreover, we show that a receptor of innate immunity, CD14, which is a part of the lipopolysaccharide receptor complex on monocyte APC, is an efficient target. For construction of CD14-specific Troybodies, we used rearranged variable(diversity)joining regions cloned from the 3C10 mouse B cell hybridoma. As a model T cell epitope, amino acids 40–48 of mouse C, presented on human leukocyte antigen-DR4, were inserted into a loop connecting ß-strands in C_H1 of human 3. In the presence of monocytes, CD14-specific Troybodies were >100 times as efficient as a nontargeting control antibody (Ab) at stimulating C^40–48-specific/DR4-restricted T cells. Presentation was dependent on the conventional processing pathway for presentation on major histocompatibility complex (MHC) class II molecules. Enhanced presentation of the C epitope was most likely a result of increased loading of MHC class II molecules, as the CD14-specific monoclonal Ab 3C10 did not induce maturation of the APC. The results show that CD14, a receptor of innate immunity, may be a promising target of recombinant Ig-based vaccines for elicitation of T cell responses in humans.

Key Words: antigen presentation • monocyte • CD4⁺ T cells • Ab • MHC class II

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