Discordant requirements for CD11c+ APCs in priming CD8 T cell responses against H-2Kb versus H-2Db restricted TMEV-associated peptides

• Published in: The Journal of immunology (1950) 2020-05, Vol.204 (1_Supplement), p.72-72.4
• Main Authors: Tritz, Zachariah Peter, Orozco, Robin, Malo, Courtney, Ayasoufi, Kathy, Yokanovich, Lila, Goddery, Emma, Khadka, Roman, Fain, Cori, Hansen, Michael, Jin, Fang, Johnson, Aaron J
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.204.Supp.72.4

CD8 T cell priming after viral infection of the central nervous system (CNS) is incompletely understood. In peripheral infections, T cell priming generally relies upon stimulation by antigen-bearing dendritic cells (DCs) migrating into draining lymph nodes. The parenchyma of the brain, however, is largely devoid of dendritic cells and evidence demonstrating that activated DCs leave the brain parenchyma is lacking. We therefore sought to understand the role of DCs and specific MHC class I molecules in priming CD8 T cells following CNS infection. We employed H-2Db−/− H-2Kb−/− (MHC-I deficient) mice that express a floxed H-2Db or floxed Kb molecule, a unique transgenic mouse system developed by our research program. Crossed with an MHC class I deficient CD11c-Cre expressing animal results in DC-specific ablation of Db or Kb Class I restricted antigen presentation ability. We found that CD11c+ APCs are critical for the early priming of CD8 T cells against the Db restricted VP2121–130 epitope of the model pathogen, TMEV. However, DCs are ultimately dispensable for long-term development of these antigen specific T cells. Discordantly, the loss of MHC class I restricted antigen presentation ability on CD11c+ APCs does not impact the priming of T cells against the H-2Kb restricted OVA257–264 epitope following intracranial TMEV-OVA infection, but does impact the ability of these T cells to successfully occupy the CNS. This work suggests that differing patterns of MHC class I restriction for CNS pathogen-derived epitopes might have functional consequences on the APC requirements for a successful CD8 T cell response against neurotropic viruses.