The magnitude of a virus-specific memory CTL population can dramatically influence the outcome of secondary infections, yet little is known about the determinants of memory size. We investigated the impact of epitope levels on CTL memory generation by using a recombinant vaccinia virus system that allows for a broad range of epitope expression with the same infectious dose of virus. The size of...

The development of nonviral, peptide-based constructs able to elicit protective in vivo CTL responses represents a major challenge in the design of future vaccines. We report the design of branched peptide delivery vehicles, termed loligomers, that facilitate the import, processing, and presentation of CTL epitopes onto nascent MHC class I molecules. These complexes are then effectively display...

RNA viruses undergo rapid sequence variation as the result of error-prone RNA replication mechanisms. When viable mutations arise in RNA regions encoding B or T cell epitopes, mutant viruses that can evade immune detection may be selected. In the carefully studied CTL response to the Gag p11C(C-M) epitope in SIVmac-infected Mamu-A*01(+) rhesus monkeys, it has been shown that CTL recognition of ...

We tested seven human immunodeficiency virus-infected children for their cytotoxic T-lymphocyte (CTL) activities towards the p24gag QASQEVKNW epitope and its nine variant sequences. Our data confirm that most, but not all, CTL responses are broadly cross-specific. For the first time, we show the high interpatient variability in cross-recognition of mutant CTL epitopes. These interindividual var...

We report here the development of multivalent T7 bacteriophage nanoparticles displaying an immunodominant H-2k(d)-restricted CTL epitope derived from the rat HER2/neu oncoprotein. The immunotherapeutic potential of the chimeric T7 nanoparticles as anti-cancer vaccine was investigated in BALB/c mice in an implantable breast tumor model. The results showed that T7 phage nanoparticles confer a hig...

Viruses can exploit a variety of strategies to evade immune surveillance by cytotoxic T lymphocytes (CTL), including the acquisition of mutations in or adjacent to CTL epitopes. Recently, an amino acid substitution (R384G) in an HLA-B*2705-restricted CTL epitope in the influenza A virus nucleoprotein (nucleoprotein containing residues 383 to 391 [NP(383-391)]; SRYWAIRTR, where R is the residue ...

CTL are important for virus clearance but also contribute to immunopathology after the infection of BALB/c mice with respiratory syncytial virus (RSV). The pulmonary immune response to RSV is dominated by a CTL population directed against the CTL epitope M2-1 82-90. Infection with a virus carrying an M2-1 N89A mutation introduced by reverse genetics failed to activate this immunodominant CTL po...

Immune pressure on lentiviruses exerted by cytotoxic T lymphocytes (CTL) selects for virus CTL epitope mutations. Currently employed methods for monitoring emerging CTL epitope mutations rely on the labor-intensive and time-consuming techniques of virus population or clonal sequencing. Here we describe the development of a high-throughput quantitative reverse transcription-PCR assay that facili...

The molecular anatomy of an immunodominant, Ld restricted CTL epitope located between residues 28-39 in hepatitis B surface Ag was defined to explore the immunologic constraints on mutational escape from the CTL response during a viral infection. Using a panel of hepatitis B surface Ag residue 28-39-specific CTL clones, the response to this epitope was found to be extremely diverse at the level...

Epitope spreading has been best characterized as an exacerbating factor in CD4(+) T cell-dependent autoimmune disease models and is believed to occur via presentation of antigens liberated by tissue destruction initiated by CD4(+) T cells specific for a primary epitope. The growing evidence that exogenous antigens can also be processed and presented by class I MHC molecules has suggested that e...