Background: The immune system has evolved to make repertoires of peptides processed from self and foreign proteomes, which are displayed in antigen-binding grooves of major histocompatibility complex (MHC) proteins and scrutinized by T cells.These antigenic peptides are termed Naturally Processed Peptides or Naturally Presented Peptides (NPPs), which play a major role in cell-mediated immunity and rational vaccine design.Therefore, it is very desirable to develop accurate methods for the prediction of NPPs from a given protein antigen or from a set of MHC-binding peptides.