International Immunology, Vol. 12, No. 5, 647-657,
May 2000
© 2000 Japanese Society for Immunology
Glycine-rich cell wall proteins act as specific antigen targets in autoimmune and food allergic disorders
1 Department of Clinical and Experimental Medicine, University of Verona, 37134 Verona, Italy
2 DIMES, Department of Experimental Medicine, and
3 Department of Clinical and Experimental Oncology, University of Genova, 16132 Genova Italy
4 CBA/ABC Advanced Biotechnology Center, 16132 Genova, Italy
5 Institute of Plant Biology, University of Zurich, 8008 Zurich, Switzerland
Correspondence to: A. Puccetti, Unità di Citologia Molecolare–Unità Monoclonali B3, Advanced Biotechnology Center, Largo Rosanna Benzi 10, 16132 Genova, Italy
Our objective was to investigate the presence of a B and T cell immune response directed against the glycine-rich cell wall protein (GRP) in patients with different autoimmune disorders and with food allergy. GRP is an ubiquitous food protein that has high homology with cytokeratins and other self proteins [Epstein–Barr virus nuclear antigen-1 (EBNA-I), heterogeneous nuclear ribonucleoprotein, fibrillar collagen] which are common targets in autoimmune disorders. A peptide (GGYGDGGAHGGGYGG) derived from GRP was used to screen human sera in direct and competitive ELISA assay. Anti-GRP-specific IgG were analyzed for their ability to cross-react with autoantigens. The intracellular cytokine profiles of the peptide-specific T cell clones obtained from representative patients have been studied. BALB/c mice were immunized with the peptide coupled to the carrier protein keyhole limpet hemocyanin (KLH). Serum IgG antibodies directed against the GRP peptide were detected in several autoimmune disorders and in food allergic patients, and were able to cross-react with autoantigens including keratin, collagen and EBNA-I. Twenty-five T cell clones showed a specific proliferative response to the GRP peptide and were of the Th0 phenotype. Eight of the 10 BALB/c mice immunized with the peptide coupled to KLH developed an autoimmune response. Our data suggest that phylogenetically highly conserved epitopes in plants, viruses and humans may be responsible for an autoimmune response in susceptible individuals. They also indicate that the antigen spreading of a particular sequence among apparently divergent proteins may participate to initiate or amplify an immune response.
Keywords: autoantigens, glycine-rich protein, random peptide library
The first two authors contributed equally to this work