Do antigenic peptides have a unique sense of direction inside the MHC binding groove? A molecular modelling study

Abstract

In the models suggested recently for antigenic peptides binding in the ~, ~, groove of MHC class I molecules, the orientation of the peptide has been shown uniquely as: the N~C vector of the peptide being parallel to the N~C vector of the ~t~ helix of MHC, Here, v~e demonstrate ~hat the reverse orientation of the peptide is equally probable. This hypothesis is supported by molecular modelling calculations and computer graphic analyses on a routine class I MHC molecule H-SK ° and its complexes with a restricted peptide RYLENGKETLQ. Analysis of the complementary interactions between the peptid¢ residues and the amino acid side chains lining the MHC groove shows that the binding orientation of the peptide may be allele-specific and could depend on the sequence and structure of" the antigenic epitope.