Memory potential is determined by priming epitope number
EMSL Project ID
48027
Abstract
Immunization with an engineered H1N1 influenza A virus disrupted for two dominant CD8+ T cell epitopes led to substantially increased subdominant responses following respiratory challenge with the comparable “knockout” or wildtype H3N2 virus. Conversely, challenge with the knockout virus following wildtype priming did not result in similar enhanced subdominant expansion. The basis of this compensatory effect is thus established at the time of primary infection, though there were no obvious differences in memory T cell numbers prior to secondary virus challenge or in the kinetics and magnitude of subdominant antigen presentation. The enhanced recall responses were, however, modified in both breadth and character. Single cell analysis of subdominant TCR CDR3? regions showed greater evidence of sharing between knockout-primed mice indicative of broader memory repertoire recruitment, in contrast to the more “private” response characteristic of the wildtype infection. The expanded subdominant CD8+ T cell populations in the knockout-primed mice also had a lower overall TCR avidity and persisted into secondary memory compartment. Thus, priming in the context of fewer epitopes recruits a broad repertoire with increased memory potential, suggesting possibilities for vaccination protocols skewed towards minor epitopes that might, for example, be less susceptible to immune escape.
Project Details
Project type
Limited Scope
Start Date
2013-04-20
End Date
2013-06-20
Status
Closed
Released Data Link
Team
Principal Investigator