Quantitation of peptide anchor residue contributions to class I major histocompatibility complex molecule binding.
Class I major histocompatibility complex molecules play an important role in cellular immunity by presenting antigenic peptides to cytotoxic T cells. Deep polymorphic pockets in the peptide-binding groove of class I major histocompatibility complex molecules provide structural complementarity for peptide "anchor" side chains. However, the minimum requirements of a peptide for high-affinity binding and the contribution of anchor side chains to binding have not been determined yet. To address these issues, we have compared the affinities of various octapeptides for purified, soluble H-2Kb molecules. The results revealed that at least 2 anchor residues are necessary for high-affinity binding, and that high-affinity binding occurs only when anchor side chains are optimally packed within the groove. The estimated free energy contribution of two anchor side chains to binding is unexpectedly large and comparable with that of peptide backbone, suggesting a crucial role of anchor residues in high-affinity, and hence specific, binding to class I molecules.
Saito
Y
Y
Department of Immunology, Scripps Research Institute, La Jolla, California 92037.
Peterson
P A
PA
Matsumura
M
M
D000409:Alanine / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002478:Cells, Cultured; D004331:Drosophila melanogaster / Q000235:genetics; D006183:H-2 Antigens / Q000378:metabolism*; D007930:Leucine / Q000378:metabolism; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000737:chemistry / Q000378:metabolism*; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D013816:Thermodynamics
D006183:H-2 Antigens; C032876:H-2Kb protein, mouse; D009842:Oligopeptides; D010446:Peptide Fragments; D007930:Leucine; D000409:Alanine