Increasing viral dose causes a reversal in CD8 T cell immunodominance during primary influenza infection due to differences in antigen presentation, T cell avidity, and precursor numbers

Abstract

T cell responses are characterized by the phenomenon of immunodominance (ID), whereby peptide-specific T cells are elicited in a reproducible hierarchy of dominant and subdominant responses. However, the mechanisms that give rise to ID are not well understood. We investigated the effect of viral dose on primary CD8+ T cell (TCD8+) ID by injecting mice i.p. with various doses of influenza A virus and assessing the primary TCD8+ response to five dominant and subdominant peptides. Increasing viral dose enhanced the overall strength of the TCD8+ response, and it altered the ID hierarchy: specifically, NP366-374 TCD8+ were dominant at low viral doses but were supplanted by PA224-233 T CD8+ at hig..