Class I and class II MHC bind self peptide sets that are strikingly different in their evolutionary characteristics

Comparison of peptides eluted from human class I and class II major histoco mpatibility complex (MHC) molecules and the proteins from which they are de rived (source proteins) revealed that class I MHC bind peptides derived fro m proteins that are highly conserved, hydrophilic, and universally expresse d, while the peptides themselves are hydrophobic and even more conserved th an their source proteins. In contrast, source proteins for class II-bound p eptides were not significantly more conserved than a random sample of prote ins. Class II-bound peptides were generally more conserved than their sourc e proteins but were significantly less conserved than class I-bound peptide s. The characteristics of class I-bound peptides can probably be explained by the selectivity of processing and transport of peptides for binding by c lass I, while the relative lack of selectivity of peptide binding for class II may explain the high incidence of autoimmune diseases associated with a lleles of these molecules.