Characterisation of a novel antigen presenting cell
Antigen presentation is crucial for generating an immune response. It is responsible for initiating full-blown immunity leading to antigen eradication, as well as the tolerogenic deletion of antigen-reactive lymphocytes for life. With such an important role, a high priority must be placed on determining how antigen presentation leads to such disparate outcomes.
Dendritic cells are regarded as the most important population of antigen presenting cells with numerous sub-populations having distinct functional capabilities. Given the potential to use dendritic cells as immunotherapy vectors, an in-depth understanding of all dendritic cell subtypes, and how they function, is of great importance.
We have recently identified a novel antigen presenting cell population in murine spleen with high capacity to cross-present antigen to CD8+ T cells. These cells resemble a myeloid dendritic-like cell that we can generate from progenitors in spleen tissues in in vitro long-term cultures and appear to be an in vivo equivalent of these cells. Preliminary evidence has shown that this cell type expresses dendritic cell markers and functions, being CD80/86+, CD11c+, CD11b+ and highly endocytic. However, they are unusual in that they only weakly express MHC-Class II and are very poor stimulators of CD4+ T cells. Both LTC-DC and their in vivo counterpart have high capacity to stimulate CD8+ T cells, particularly upon exposure to ‘danger’ signals. They are also functionally and phentoypically distinct from monocytes, and the known conventional and plasmacytoid DC subsets.
This led us to the hypothesis that this novel APC subset was positioned to have ready access to blood-borne antigen, and may play a unique role in antigen cross-presentation to CD8+ T cells and in T-independent B cell immunity.
The overall aim of this project is to characterise these cells more fully in relation to other known DC and myeloid cell types. We are investigating the capacity of these cells to activate T cell immunity and are investigating whether they participate in T-independent B cell immunity.