Amino acid preferences in the octapeptide subunit of the major histocompatibility complex class I heterotrimer H-2Ld.
Major histocompatibility complex class I (MHC-I) molecules are heterotrimers composed of polymorphic alpha-chains, monomorphic beta-chains, and peptides of eight or nine amino acids. The peptides are derived from various intracellularly occurring proteins and are very heterogeneous. They are essential for a stable conformation of the MHC-I protein at physiological temperature. This study presents results from stabilization experiments that were designed to determine the impact of the amino acids in every sequence position of octapeptides on the thermal stability of the mouse MHC-I molecule H2-Ld. OX7 octapeptide libraries with one defined and seven randomized positions were employed as they allow the effects of individual amino acids to be determined. The results confirm the importance of the motif amino acids proline and leucine for positions 2 and 8, respectively, of octapeptides. They are among the most efficient amino acids for these positions. However, with a few exceptions, all amino acids are permitted in all eight sequence positions. Hydrophobic amino acids are generally favored. Charged amino acids, especially aspartic acid and glutamic acid, are disfavored. Stabilization indices were defined as measures for the MHC stabilization power of the amino acids. These indices can serve to predict the efficiency of peptide binding to H-2Ld and can guide the design of T-cell epitopes.
Pridzun
L
L
Max-Planck-Institut für Biologie, Abteilung Immungenetik, Tübingen, Germany.
Wiesmüller
K H
KH
Kienle
S
S
Jung
G
G
Walden
P
P
D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation; D006183:H-2 Antigens / Q000737:chemistry* / Q000378:metabolism; D064532:Histocompatibility Antigen H-2D; D006358:Hot Temperature; D008285:Major Histocompatibility Complex; D051379:Mice; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D013329:Structure-Activity Relationship
D006183:H-2 Antigens; C032876:H-2Kb protein, mouse; D064532:Histocompatibility Antigen H-2D; D009842:Oligopeptides