CHIMERIC PEPTIDES - A NEW APPROACH TO ENHANCING THE IMMUNOGENICITY OFPEPTIDES WITH LOW MHC CLASS-I AFFINITY - APPLICATION IN ANTIVIRAL VACCINATION

Recruitment of the CTL repertoire specific for subdominant epitopes th at have a low MHC class I-binding affinity could be the way to achieve an efficient protective immunity against spontaneous tumors and virus es with high mutation rate, However, we have reported recently that su bdominant peptides of influenza A Puerto Rico/8/34 (flu PR8) nucleopro tein (NP) with low Db affinity are only partially able to protect mice against lethal influenza infection, This seems to be due to their ina bility to recruit the specific CTL repertoire, and suggests that subdo minant peptides could be used for vaccination only if they become high ly immunogenic, in this work, we describe an approach that allows enha ncement of the immunogenicity of every low affinity peptide presented by the Db molecule, It consists in producing chimeric peptides compose d by amino acids from a high Db affinity peptide (NP366) in positions that interact with the MHC, and amino acids from low Db affinity nonim munogenic influenza NP-derived peptides (NP17, NP97, NP330, and NP469) in positions that are exposed to the TCR, All chimeric peptides teste d exhibited a high Db affinity and efficiently recruited the CTL reper toire specific for the corresponding low Db affinity peptide, Furtherm ore, vaccination with chimeric peptides that corresponded to subdomina nt NP17 and NP97 peptides induced a very potent anti-flu PR8 protectiv e immunity.