THE IMPORTANCE OF SECONDARY ANCHOR RESIDUE MOTIFS OF HLA CLASS-I PROTEINS - A CHEMOMETRIC APPROACH

In this paper we report a chemometric approach to Quantitative Structu re-Activity Relationship (QSAR) analysis applied to a study of the bin ding of peptides to Major Histocompatibility Complex (MHC) class I pro teins. Peptides which possess the known primary anchor residue motif f or HLA-B27 binding do not necessarily bind to HLA-B27 proteins. Second ary anchor residues are also involved, but it is not yet clear which a mino acids are required or in which positions. A classic approach to t his problem would be to synthesize multiple peptides each varying by a single amino acid from a starting peptide, and test them for their bi nding properties. Not only is this approach inefficient, but it is ess entially unable to provide information about possible mutual interacti ons of amino acid residues in different positions. Using a statistical design to select the most informative compounds to use in the QSAR st udy, it was possible to analyse the effects on HLA-B27 peptide binding of different amino acids in four positions by means of only nine pept ides. The relative binding activity of these peptides could then be mo deled mathematically to provide information about the relative contrib ution of each of the four positions and to suggest a new peptide with high binding affinity. Our results demonstrate the usefulness of the c hemometric strategy for studying peptides of interest in molecular imm unology.