Molecular mimicry of phage displayed peptides mimicking GD3 ganglioside

We have analyzed sequence homologies between nonimmunogenic phage displayed peptides mimicking GD3 ganglioside and human/ mouse self-proteins. The GD3 ganglioside phagotopes showed homology to proteins involved in carbohydrat e metabolism/transport. Besides this expected homology, molecular mimicry o f critical regulatory proteins was found. These data contribute to our unde rstanding of the structural relatedness of antigenic determinants defined b y specific anti-GD3 monoclonal antibodies and, in addition, suggest that mo lecular mimicry might explain the nonimmunogenicity of these peptides other wise characterized by specificity to the mAb counterpart. We conclude that construction of peptides harboring motifs absent or scarcely represented in endogenous self-proteins might be a useful approach in melanoma immunother apy. (C) 1999 Elsevier Science Inc. All rights reserved.