1. Academic Validation
  2. Human CD14 is an efficient target for recombinant immunoglobulin vaccine constructs that deliver T cell epitopes

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

  • J Leukoc Biol. 2005 Mar;77(3):303-10. doi: 10.1189/jlb.0804480.
Gro Tunheim 1 Karoline W Schjetne Agnete B Fredriksen Inger Sandlie Bjarne Bogen
Affiliations

Affiliation

  • 1 University of Oslo and Rikshospitalet University Hospital, N-0027 Oslo, Norway. gro.tunheim@medisin.uio.no
Abstract

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 Ckappa, presented on human leukocyte antigen-DR4, were inserted into a loop connecting beta-strands in C(H)1 of human gamma3. In the presence of monocytes, CD14-specific Troybodies were >100 times as efficient as a nontargeting control antibody (Ab) at stimulating Ckappa(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 Ckappa 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.

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