MHC class I-restricted CD8 T lymphocyte epitopes are consisted of anchor motifs, TCR contact residues and the peptide backbone. A serial variant epitopes with substitution of amino acids at either anchor motifs or TCR contact residues have been synthesized for specific IFN-gamma responses to clarify the TCR recognition mechanism as well as to assess the epitope prediction capacity of immunoinformatical programmes. CD8 T lymphocytes recognise the steric configuration of functional groups at the TCR contact side chain with a parallel observation that peptide backbones of various epitopes adapt to the conserved conformation upon binding to the same MHC class I molecule. Variant epitopes with amino acid substitutions at the TCR contact site are not recognised by specific CD8 T lymphocytes without compromising their binding capacity to MHC class I molecules, which demonstrates two discrete antigen presentation events for the binding of peptides to MHC class I molecules and for TCR recognition. The prediction outcome of immunoinformatical programmes is not consistent with results of epitope identification with laboratory experiments in the absence of information on the interaction with TCR contact residues. Immunoinformatical programmes based on the binding affinity to MHC class I molecules are not sufficient for the accurate prediction on CD8 T lymphocyte epitopes. The predictive capacity is further improved to distinguish mutant epitopes from the non-mutated one if the peptide-TCR interface is integrated into the computing simulation programme.
