'Troy-bodies': antibodies as vector proteins for T cell epitopes

Biomol Eng. 2001 Oct 15;18(3):109-16. doi: 10.1016/s1389-0344(01)00091-0.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies / genetics
  • Antibodies / immunology*
  • Antibody Specificity
  • Antigen-Presenting Cells / immunology*
  • Epitopes / immunology*
  • Histocompatibility Antigens Class II / immunology
  • Humans
  • Immunoglobulin D / immunology
  • Immunoglobulin Variable Region / chemistry
  • In Vitro Techniques
  • Mice
  • Mice, Inbred BALB C
  • Models, Structural
  • Mutagenesis, Insertional
  • Nitrohydroxyiodophenylacetate
  • Protein Engineering*
  • Protein Folding
  • Protein Structure, Tertiary
  • Recombinant Proteins / immunology
  • T-Lymphocytes / immunology*

Substances

  • Antibodies
  • Epitopes
  • Histocompatibility Antigens Class II
  • Immunoglobulin D
  • Immunoglobulin Variable Region
  • Recombinant Proteins
  • Nitrohydroxyiodophenylacetate