AMINO-ACID PREFERENCES IN THE OCTAPEPTIDE SUBUNIT OF THE MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-I HETEROTRIMER H-2L

Major histocompatibility complex class I (MHC-I) molecules are heterot rimers composed of polymorphic alpha-chains, monomorphic beta-chains, and peptides of eight or nine amino acids. The peptides are derived fr om various intracellularly occurring proteins and are very heterogeneo us. They are essential for a stable conformation of the MHC-I protein al physiological temperature. This study presents results from stabili zation experiments that were designed to determine the impact of the a mino acids in every sequence position of octapeptides on the thermal s tability of the mouse MHC-I molecule H2-L(d). OX(7) octapeptide librar ies with one defined and seven randomized positions were employed as t hey allow the effects of individual amino acids to be determined. The results confirm the importance of the motif amino acids proline and le ucine for positions 2 and 8, respectively, of octapeptides. They are a mong 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 ami no acids, especially aspartic acid and glutamic acid, are disfavored. Stabilization indices were defined as measures for the MHC stabilizati on power of the amino acids. These indices can serve to predict the ef ficiency of peptide binding to H-2L(d) and can guide the design of T-c ell epitopes.