Modeling the adaptive immune system: predictions and simulations

Lundegaard, Claus; Lund, Ole; Kesmir, Can; Brunak, Søren; Nielsen, Morten

In the early 1980s, Hopp and Woods (Hopp and Woods, 1981, 1983 ) developed the first linear epitope prediction method. This method takes the assumption that the regions of proteins that have a high degree of exposure to solvent contain the antigenic determinants. According to the hydrophilicity scale generated by Levitt (1976) , Hopp and Woods (1981) assigned the hydrophilicity propensity to each amino acid in a sequence and looked at groups of six residues. This gave promising results and a number of methods have since been developed with the aim of predicting linear epitopes using a combination of different amino acid propensities (Alix, 1999; Debelle et al., 1992; Jameson and Wolf, 1988; Maksyutov and Zagrebelnaya, 1993; Odorico and Pellequer, 2003; Parker et al., 1986) . , Pellequer et al. (1993 proposed an evaluation set containing 85 continuous epitopes in 14 proteins and found that the method based on turn propensity (i.e. the propensity of an amino acid to occur within a turn structure) had the highest sensitivity using this set. Seventy percent of the residues predicted to be in epitopes by this method were actually part of epitopes. The sensitivity for methods based on other propensities was in the range of 36-61% (Pellequer et al., 1991) . Analyzing the epitope regions in the Pellequer dataset reveals that almost all the hydrophobic amino acids are underrepresented, supporting the assumption that linear B-cell epitopes will occur in hydrophilic regions of the proteins.