Vanessa E. Prescott, Peter M. Campbell, Andrew Moore, Joerg Mattes, Marc E. Rothenberg, Paul S. Foster, T. J. V. Higgins, and Simon P. Hogan*

Division of Molecular Bioscience, The John Curtin School of Medical Research, Australian National University, Canberra, ACT, Australia, Division of Allergy and Immunology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio 45229, and Divisions of Entomology and Plant Industry, Commonwealth Scientific and Industrial Research Organization, Canberra, ACT, Australia

Abstract:

The development of modern gene technologies allows for the expression of recombinant proteins in non-native hosts. Diversity in translational and post-translational modification pathways between species could potentially lead to discrete changes in the molecular architecture of the expressed protein and subsequent cellular function and antigenicity. Here, we show that transgenic expression of a plant protein (-amylase inhibitor-1 from the common bean (Phaseolus vulgaris L. cv. Tendergreen)) in a non-native host (transgenic pea (Pisum sativum L.)) led to the synthesis of a structurally modified form of this inhibitor. Employing models of inflammation, we demonstrated in mice that consumption of the modified AI and not the native form predisposed to antigen-specific CD4+ Th2-type inflammation. Furthermore, consumption of the modified AI concurrently with other heterogeneous proteins promoted immunological cross priming, which then elicited specific immunoreactivity of these proteins. Thus, transgenic expression of non-native proteins in plants may lead to the synthesis of structural variants possessing altered immunogenicity.