The alternative pathway of T cell activation: biology, pathophysiology, and perspectives for immunopharmacology.

The application of monoclonal antibodies and recombinant mediators to studies of T cell activation has led to a new concept regarding the central mechanisms underlying specific immune responses in man. Stimulation of human T cells to express their functional programs with regard to immunoregulatory activities and effector functions can be mediated through several distinct mechanisms or pathways. We report on the recently discovered T3-Ti antigen receptor independent mode of human T cell activation, namely, the T11-mediated "alternative pathway." Recent evidence supports the notion that this pathway plays an important role in the immune response in man and that failure to activate T cells through T11 is associated with immunodeficiency. The characterization of functional epitopes of the T11 molecule along with functional investigations on patients suffering from etiologically different cases of immunodeficiency provides important perspectives for future pharmacological interventions into the human immune system. It seems likely that immunologic disorders such as autoimmune disease and immunodeficiencies result from overamplification or blockades of the "alternative pathway of T cell activation" and that the T11 epitope represents a potential site for selective inhibition of the "alternative pathway of T cell activation," e.g., by means of synthetic peptide analogues. Conversely, high affinity ligands to the T11 epitope might be suitable for immunostimulation immunodeficiencies that result from circulating blocking factors of the LFA-3/T11 interaction.