Faculty of Engineering and Natural Sciences
Super Peptides: combined structural and biochemical design of a peptidebased vaccine
Adil Doganay Duru
Karolinska Institute, Sweden
Abstract: Lymphocytic choriomeningitis virus infection of H-2b mice generates a strong CD8+ CTL response mainly directed toward three immunodominant epitopes, one of which, gp33, is presented by both H-2Db and H-2Kb MHC class I molecules. CTL response against gp33 acts as a selective agent for the emergence of viral escape variants. Virus by introducing point mutations creates altered peptide ligands (APLs) that, when presented by class I MHC molecules, antagonize CTL recognition and ultimately allow the virus to evade the cellular immune response. The emergence of APLs of the gp33 epitope is particularly advantageous for LCMV, as it allows viral escape in the context of both H-2Db and H-2Kb MHC class I molecules. Modifying APLs and escape variants is an effective way to circumvent these problems. However, generating enhanced binding of altered peptides to class I MHC molecules and extended peptide-MHC cell surface stability while still maintaining recognition of the wild-type peptide is not straightforward. Many research groups have designed these peptides by substituting the observed anchor residues with those that are most preferred by the MHC molecule. Unfortunately this approach does not work for many antigenic peptides. Here in this study we are introducing a modification that modulates and increases overall CTL responses through the use of a novel non-dogmatic approach that results in the design of agonistic Super-Peptide of otherwise antagonistic altered escape epitopes.
December 24 (Wednesday), 2008, 14:30, FENS L048