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

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Abstract
In the models suggested recently for antigenic peptides binding in the α1, α2 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 α1, helix of MHC. Here, we demonstrate that the reverse orientation of the peptide is equally probable. This hypothesis is supported by molecular modelling calculations and computer graphic analyses on a murine class I MHC molecule H‐2Kd and its complexes with a restricted peptide RYLENGKETLQ. Analysis of the complementary interactions between the peptide 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.