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

oleh: Miaojuan Huang, Rong Xu, Cristina Triffon, Nicole Mifsud, Weisan Chen

Format: Article
Diterbitkan: MDPI AG 2021-06-01

Deskripsi

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<sup>+</sup> 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<sup>+</sup> T cell response to IAV infection. We show CD8<sup>+</sup> 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<sub>319–330</sub><sup>#</sup> (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<sub>124–134</sub>, M2<sub>7–15</sub>, NA<sub>337–346</sub>, PB2<sub>39–49</sub>, HA<sub>445–453</sub> and NS1<sub>195–203</sub>). Additionally, most of these novel epitopes are highly conserved among H1N1 and H3N2 strains that circulated in Australia and other parts of the world.