B and T lymphocytes are crucial for protective immune responses against infectious diseases and cancer but may also cause autoimmune diseases. B and T cells recognize infectious antigens or cancer antigens by use of highly specific receptors. It is well established that B and T cells mutually stimulate each other (collaborate) by joint recognition of the same antigen. The mechanism appears to be that while the B cell receptors recognize antigen in the extracellular fluid, T cells recognize fragments of the antigen bound to Major Histocompatibility Complex (MHC) molecules on the B cell surface. Our studies have, added to this picture: the B cell receptors, immunoglobulins, are themselves partially degraded and short fragments derived from the Variable regions are presented on MHC molecules to T cells. By this mechanism B cells can themselves present their unique V-regions (idiotopes, Id) to T cells, a phenomenon that forms the basis for a novel type of Id-dependent T-B collaboration (Munthe et al 2004). Excessive Id-dependent T-B collaboration appears to cause production of autoantibodies and autoimmune disease. The mechanism is that self reactive B cells receive help from Id-specific T cells, thereby circumventing a lack of conventional T cell help (due to T cell tolerance for self antigen).

Id-specific T cells not only help normal B cells and cause autoimmunity, but can also directly recognize V region peptides on MHC molecules on B lymphoma cells and initiate a lethal attack (Lundin et al. Blood 2003). Id-specific T cells can also kill multiple myeloma cells (Dembic et. al. PNAS 2000, Blood 2001). In this case monoclonal immunoglobulins abundantly secreted by the tumor cells are picked up and presented by MHC molecules on professional antigen presenting cells like dendritic cells infiltrating the cancer tissue. This results in activation of Id-specific T cells and an indirect killing of myeloma cells.

We have exploited the fact that fragments of antibodies are presented on MHC molecules by developing recombinant immunoglobulin-based vaccines that target genetically integrated T cell epitopes to antigen presenting cells that initiate immune responses. A first generation of vaccines, called Troybodies (Lunde et. al., Nature Biotech), only have the ability to stimulate T cell responses. A second generation of vaccines, called Vaccibodies, can stimulate both B and T cell responses. The Ig-based vaccines are delivered as DNA vaccines and are genetically equipped with V-regions that target them to receptors of the innate immune system for induction of potent immune responses (Schjetne et al. 2003).