The farther the better: investigating how distance from human self affects the propensity of a peptide to be presented on cell surface by MHC class I molecules, the case of Trypanosoma cruzi.

More than twenty years ago the reverse vaccinology paradigm came to light trying todesign new vaccines based on the analysis of genomic information in order to selectthose pathogen peptides able to trigger an immune response. In this context, focusingon the proteome of Trypanosoma cruzi, we investigated the link between theprobabilities for pathogen peptides to be presented on a cell surface and their distancefrom human self. We found a reasonable but, as far as we know, undiscoveredproperty: the farther the distance between a peptide and the human-self the higherthe probability for that peptide to be presented on a cell surface. We also found thatthe most distant peptides from human self bind, on average, a broader collection ofHLAs than expected, implying a potential immunological role in a large portion ofindividuals. Finally, introducing a novel quantitative indicator for a peptide tomeasure its potential immunological role, we proposed a pool of peptides that could bepotential epitopes and that can be suitable for experimental testing. The software tocompute peptide classes according to the distance from human self is free available athttp://www.iasi.cnr.it/~dsantoni/nullomers.