Discordant rearrangement of primary and anamnestic CD8+ T cell responses to influenza A viral epitopes upon exposure to bacterial superantigens: Implications for prophylactic vaccination, heterosubtypic immunity and superinfections

• DOI: 10.1371/journal.ppat.1008393
• Publication Date: 2020-05-20T17:24:19Z
• Authors: Courtney E. Meilleur; Arash Memarnejadian; Adil N. Shivji; Jenna M. Benoit; Stephen W. Tuffs; Tina S. Mele; Bhagirath Singh; Jimmy D. Dikeakos; David J. Topham; Hong-Hua Mu; Jack R. Bennink; John K. McCormick; S. M. Mansour Hae...
• Keywords: Immunodominance

Infection with (SAg)-producing bacteria may precede or follow infection vaccination against influenza A viruses (IAVs). However, how SAgs alter the breadth of IAV-specific CD8+ T cell (TCD8) responses is unknown. Moreover, whether recall mediating heterosubtypic immunity to IAVs are manipulated by remains unexplored. We employed wild-type (WT) and mutant bacterial SAgs, SAg-sufficient/deficient Staphylococcus aureus strains, WT, mouse-adapted reassortant IAV strains in multiple vivo settings address above questions. Contrary popular view that delete anergize cells, systemic administration staphylococcal enterotoxin B (SEB) Mycoplasma arthritidis mitogen before intraperitoneal immunization enlarged clonal size 'select' TCD8 reshuffled hierarchical pattern primary responses. This was mechanistically linked TCR Vβ makeup impacted clones rather than their immunodominance status. Importantly, SAg-expanded retained IFN-γ production cognate cytolytic capacities. The enhancing effect SEB on immunodominant also evident heat-inactivated live attenuated administered intramuscularly intranasally, respectively. Interestingly, prime-boost settings, outcome depended strictly upon time point at which this SAg introduced. Accordingly, injection priming raised CD127highKLRG1low memory precursor frequencies augmented anamnestic SEB-binding TCD8. By comparison, introducing boosting diminished IAV-derived epitopes drastically indiscriminately. accompanied lower Ki67 higher Fas, LAG-3 PD-1 levels consistent a pro-apoptotic and/or exhausted phenotype. Therefore, can have contrasting impacts anti-IAV depending naïve/memory status composition exposed Finally, local SEB-producing S. enhanced pulmonary IAV. Our findings clear implications for superinfections prophylactic vaccination.