Have we cut ourselves too short in mapping CTL epitopes?

MHC class I molecules generally present peptides of eight to ten amino acids; however, peptides of 11–14 residues can also elicit dominant cytotoxic T lymphocyte responses, sometimes at the expense of overlapping shorter peptides. Although long-bulged epitopes are considered to represent a barrier for T cell receptor recognition, recent structural data reveal how these super-bulged peptides are engaged while simultaneously maintaining MHC restriction. We propose that algorithms widely used to predict class I-binding peptides should now be broadened to include peptides of over ten residues in length.