Batf3-dependent Dendritic Cells are Required to Present Cell-associated Antigen to CD4 T Cells

Abstract

Abstract Dendritic cells (DCs) are required to prime T cells during an immune response. The dogma in the field is that Batf3-dependent DCs (DC1s) prime CD8 T cells and IRF4-dependent DCs (DC2s) prime CD4 T cells. However, recent studies have shown that DC1s are required for induction of Th1 immune responses and to prime autroreactive CD4 T cells in the NOD mouse model of diabetes. Therefore, this segregation of priming theory is flawed. To further study the contribution of DC1s to CD4 T cell priming, we generated an XCR1-cre mouse and crossed it to the MHC class II floxed mouse to generate MHC class II deficient DC1s. We found that the form of antigen directs the priming of T cells. DC2s are superior at presenting soluble antigen as evidenced by normal CD4 and CD8 OVA specific T cell responses in mice lacking DC1s. However, DC1s are superior at presenting cell-associated antigen as evidenced by a lack of OVA specific CD4 and CD8 T cell priming in mice lacking DC1s. Furthermore, CD4 priming during tumor immune responses is absent when DC1s lack MHC class II. Our findings show that the DC subsets differ in the form of antigen that they present. DC1s present cell-associated material; whereas DC2s present soluble antigen.