Broad-Based Influenza-Specific CD8+ T Cell Response without the Typical Immunodominance Hierarchy and Its Potential Implication

Abstract

Syngeneic murine systems have pre-fixed MHC, making them an imperfect model for investigating the impact of MHC polymorphism on immunodominance in influenza A virus (IAV) infections. To date, there are few studies focusing on MHC allelic differences and its impact on immunodominance even though it is well documented that an individual’s HLA plays a significant role in determining immunodominance hierarchy. Here, we describe a broad-based CD8⁺ T cell response in a healthy individual to IAV infection rather than a typical immunodominance hierarchy. We used a systematic antigen screen approach combined with epitope prediction to study such a broad CD8⁺ T cell response to IAV infection. We show CD8⁺ T cell responses to nine IAV proteins and identify their minimal epitope sequences. These epitopes are restricted to HLA-B*44:03, HLA-A*24:02 and HLA-A*33:03 and seven out of the nine epitopes are novel (NP_319–330^# (known and demonstrated minimal epitope positions are subscripted; otherwise, amino acid positions are shown as normal text (for example NP 319–330 or NP 313–330)), M1_124–134, M2_7–15, NA_337–346, PB2_39–49, HA_445–453 and NS1_195–203). Additionally, most of these novel epitopes are highly conserved among H1N1 and H3N2 strains that circulated in Australia and other parts of the world.