Endogenous peptides of a soluble major histocompatibility complex class I molecule, H-2Lds: sequence motif, quantitative binding, and molecular modeling of the complex.
To gain insight into the rules that govern the binding of endogenous and viral peptides to a given major histocompatibility complex (MHC) class I molecule, we characterized the amino acid sequences of a set of self peptides bound by a soluble analogue of murine H-2Ld, H-2Lds. We tested corresponding synthetic peptides quantitatively for binding in several different assays, and built three-dimensional computer models of eight peptide/H-2Lds complexes, based on the crystallographic structure of the human HLA-B27/peptide complex. Comparison of primary and tertiary structures of bound self and antigenic peptides revealed that residues 2 and 9 were not only restricted in sequence and tolerant of conservative substitutions, but were spatially constrained in the three-dimensional models. The degree of sequence variability of specific residues in MHC-restricted peptides reflected the lack of structural constraint on those amino acids. Thus, amino acid residues that define a peptide motif represent side chains required or preferred for a close fit with the MHC class I heavy chain.
D000595:Amino Acid Sequence; D000818:Animals; D001667:Binding, Competitive; D002851:Chromatography, High Pressure Liquid; D000939:Epitopes / Q000737:chemistry; D006183:H-2 Antigens / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D064532:Histocompatibility Antigen H-2D; D007700:Kinetics; D008285:Major Histocompatibility Complex; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry; D011487:Protein Conformation; D017386:Sequence Homology, Amino Acid
D000939:Epitopes; D006183:H-2 Antigens; D064532:Histocompatibility Antigen H-2D; D010455:Peptides