To summarize, two novel approaches are currently being examined that allow for identification of antigen-specific T cells. A biochemical approach to generating soluble multivalent MHC complexes has been to generate tetrameric MHC complexes linked to avidin. We have also generated a general approach for producing soluble divalent versions of class I and class II MHC molecules, using Ig as a molecular scaffold. The experimental system described here outlines a general approach of using multivalent high affinity ligands to study cell-cell interactions, driven by multivalent ligand-receptor interactions. Our work indicates that divalent chimeric molecules are high-avidity analogs of proteins useful in probing and selectively regulating cellular responses.