Precursor frequency and competition dictate the HLA-A2-restricted CD8 T cell responses to influenza A infection and vaccination in HLA-A2.1 transgenic mice

Abstract

The human HLA-A2-restricted CD8+ T cell response to influenza A virus (IAV) is largely directed against the matrix proteinderived M1 58-66 epitope and represents an archetypal example of CD8+ T cell immunodominance. In this study, we examined the CD8+ T cell hierarchy to M158-66 and two subdominant IAV-specific epitopes: NS1122-130 and PA46-55 in HLA-A2+ human subjects and HLA-A2.1 transgenic (HHD) mice. Using epitope-based lipopeptides, we show that the CD8+ T cell hierarchy induced by IAV infection could also be induced by lipopeptide vaccination in a context outside of viral infection when the Ag load is equalized. In the HHD HLA-A2.1 mouse model, we show that the naive T cell precursor f..