Reverse Genetics Modification of Cytomegalovirus Antigenicity and Immunogenicity by CD8 T-Cell Epitope Deletion and Insertion
Figure 4
Principle of “orthotopic peptide swap” mutagenesis. (Top) Genome size scale of mCMV showing the genomic region of ORFs m161-m166 enlarged. ORFs are symbolized by boxes, with the blue box representing ORFm164 encoding the viral carrier protein gp36.5 [87] that includes the coding sequence for an intrinsic antigenic peptide that is immunodominant in the MHC haplotype H-2d [53]. Overlaps with neighboring ORFs are indicated by blue-striped areas. (Center) Amino acid sequences of the intrinsic peptide to be replaced (blue letters with large type size) and the replacing foreign peptide (red letters with large type size). Epitope-flanking residues in the host protein sequence are shown in blue letters with small type size. (Bottom) Artwork models illustrating the binding of the intrinsic antigenic peptide (blue chaplet) and of the inserted foreign antigenic peptide (red chaplet) to their respective presenting MHC-I molecules. Note that in the documented case, peptide swap also leads to a change in MHC-restriction.
