There is a great deal of information regarding the minimal requirements for activation of primed T cells. T cell clones can be stimulated to release granule contents and produce lymphokines by anti-CD3 antibody or purified antigen-MHC proteins. T cell hybridomas can also be stimulated to produce lymphokines by anti-CD3 antibody or purified antigen-MHC proteins. Activation of these primed T cell lines can occur in the absence of specialized presenting cells and their accessory molecules. This project is to define the minimal requirements for activation of naive T cells and to evaluate the effects of additional stimuli on the magnitude and type of T cell activation elicited. We have been successful in the activation of T cells using different activators such as: anti-CD3 antibody and purified allo-MHC molecules. The relevant cell populations in the activation are being evaluated by fluorescent activated cell sorting. We are presently studying different T cell activation parameters (lymphokine production, anergy, induction, signal transduction, and gene expression) in this sytem. We will then evaluate changes in these T cell responses caused by the deletion or addition of antigen presenting cells, lymphokines, adhesion molecules or costimulatory molecules to T cell stimulus. We have generated a recombinant soluble immune ICAM-1 for use in our experiments and will pursue the generation of other soluble adhesion/costimulatory molecules. The molecular requirements for T cell activation and the varying phenotypes of this activation are very basic to the generation of successful immunity and the modulation of aberrant immune responses.
