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 histocompatibility complex (MHC) molecules and the proteins from which they are derived (source proteins) revealed that class I MHC bind peptides derived from proteins that are highly conserved, hydrophilic, and universally expressed, while the peptides themselves are hydrophobic and even more conserved than their source proteins. In contrast, source proteins for class II-bound peptides were not significantly more conserved than a random sample of proteins. Class II-bound peptides were generally more conserved than their source proteins but were significantly less conserved than class I-bound peptides. The characteristics of class I-bound peptides can probably be explained by the selectivity of processing and transport of peptides for binding by class I, while the relative lack of selectivity of peptide binding for class II may explain the high incidence of autoimmune diseases associated with alleles of these molecules.
Yeager
M
M
Department of Biology and Institute of Molecular Evolutionary Genetics, 208 Mueller Laboratory, The Pennsylvania State University, University Park, PA 16802, USA.
Carrington
M
M
Hughes
A L
AL
D000483:Alleles; D000818:Animals; D017951:Antigen Presentation / Q000235:genetics / Q000276:immunology; D001324:Autoantigens / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D017124:Conserved Sequence / Q000235:genetics; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D019143:Evolution, Molecular; D015870:Gene Expression; D014644:Genetic Variation / Q000235:genetics; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology*; D006801:Humans; D009928:Organ Specificity; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D012377:Rodentia
D001324:Autoantigens; D018984:Epitopes, T-Lymphocyte; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D010446:Peptide Fragments