The hierarchy of two different immunodominant epitopes influences CD4+ T cell responses (APP5P.112)

Abstract

Abstract A cell-free antigen processing system for MHC class II was recently reported that has proved to be effective in identifying physiologically relevant CD4+ T cell epitopes from proteins (Hartman/Kim, et al. Nat Med. 16, pp1333-40 (2010)). This system has also provided insights into the mechanism of epitope selection (Kim, et al. Nat Commun. 5:5369 (2014)). We applied this system to a mixture of two different antigens, H5N1-HA1 and LSA-NRC of malaria to examine if there would be a competition for epitope capture. While each dominant epitope from either protein was identified in the system individually, when both proteins were simultaneously present, HA1 dominant epitope was predominantly selected. The competition between different epitopes was verified in vivo by immunizing HLA-DR1 transgenic mice with a mixture of HA1 and LSA-NRC. A recall T cell proliferation showed that T cells responded only to the HA1 and its dominant epitope. These observations did not change even when DR1 mice were immunized with increasing molar ratio of LSA-NRC to HA1 (1:1, 2:1 or 4:1). However, T cell responded to both antigens if mice were immunized first with LSA-NRC dominant epitope followed by HA1 epitope. These findings show a hierarchy for the selection of dominant epitopes from different proteins during antigen processing. Immunodominance hierarchy among different antigens influences the epitope presentation to the same MHC II, which can be important factor for designing combination vaccines.