Grant: Operating Grant

The development of vaccines remains emperical and we lack the knowledge to predict efficacy because we still lack a knowledge on the basic aspects of immune defences especially those most closely linked to pathways leading to imune activation such as antigen processing. When a viral infection occurs, immune responses are initiated by dendritic cells (DCs). DCs capture the virus and digest the virus proteins into fragments or antigens that are displayed by DCs to activate other cells of the immune system, such as T and B cells. Two pathways within the DCs help to direct the immune response to (1) activate cytolytic T cells to kill virally infected cells (termed MHC class I) or (2) activate B cells to produce antibodies (termed MHC class II). Within DCs, the protein known as CD74 (or invariant chain) is thought to exclusively push the DC response towards an MHC class II response. However, we recently demonstrated a CD74-dependent MHC class I pathway in DCs that plays a major role in the generation of MHC class I restricted responses against viruses. This was a completely novel finding and now means that CD74 plays a role in both arming antibody-producing cells (known as B cells) and also arming cells that destroy virally infected cells (known as cytolytic T cells). Prior to this, the two pathways were considered to be completely separate. We wish to further examine the exact role CD74 has within DCs. The work in this proposal has the potential to improve the predicability and efficacy of vaccines.