Infrequent Occurrence of Natural Mutations in the pp65(495–503) Epitope Sequence Presented by the HLA A∗0201 Allele among Human Cytomegalovirus Isolates

To determine if mutations of an immunodominant HLA-restricted cytomegalovirus (CMV) peptide sequence occur in nature, the sequence corresponding to the HLA A∗0201-specific peptide CMVpp65(495–503) was determined in 50 human CMV isolates. Rare mutations were detected; 6 of 50 were silent mutations at the amino terminus of the peptide, while 3 of 50 were mutations of the native methionine residue to isoleucine (M499I). The observed M499I mutation in three isolates decreased cytolytic targeting.