CD8 T cell response for H60 requires CD4 T cell help when the antigen is expressed as a viral antigen (132.36)

Abstract

Abstract CD4 helper T cell is critical for the generation of primary and memory CD8 T cells specific for non-inflammatory antigens. Minor histocompatibility antigens are representative non-inflammatory cellular antigens that require CD4 help for the response induction, and we have shown that CD8 T cell response for minor histocompatibility antigen H60 is dependent on CD4 help not only for the primary response but also for the secondary response inductions. In this study, we addressed a question whether H60 epitope as a viral antigen would require CD4 help for specific response induction. A recombinant vaccinia virus expressing H60-CD8 epitope and HY-CD4 epitope (rVV-H60HY) was used for immunization of B6 female mice. Immunization with the recombinant virus induced a significant amount of H60-specific CD8 T cell proliferation with a peak frequency around 10~20% of total blood CD8 T cells. The response was CD4 help dependent both after the primary and secondary viral challenges. The CD4 help could be substituted by combined treatment of TLR agonists and anti-CD40 antibody. Our results demonstrate that CD4 help is required for appropriate CD8 T cell responses specific for H60 not only as cellular antigen but also as viral antigen, and the signaling through TLR and CD40 would license antigen presenting cells to appropriately activate antigen-specific CD8 T cells.