1. A panel of cells designed to express normal or mutated human HLA-A0201 was constructed and used to investigate the interactions between the peptide antigen, class I major histocompatibility complex, CD8 and cytotoxic T lymphocyte antigen receptor.
2. Analysis of the extensive data generated has revealed that the optimum peptide presented to cytotoxic T lymphocytes by HLA-A0201 contains nine amino acids. It lies in the peptide-binding groove of the class I molecule, orientated from N- to C-termini, and its detailed position within the groove has been deduced. The roles of individual residues in the class I molecule in antigen presentation are described, and the site of the ligand on target cells for interaction with CD8 on cytotoxic T lymphocytes is located.