The present invention provides methods for sequentially screening for compounds with the potential to interfere with low affinity receptor-ligand contacts using an interfacial optical assay, such as surface plasmon resonance (SPR). The method comprises contacting a candidate compound with an immobilized receptor, contacting the receptor, which may or may not have the candidate compound bound to it, with the ligand and detecting by interfacial optical assay whether or not the ligand or ligand-compound complex has bound to the receptor or receptor-compound complex. If the ligand binds, the method shows that the compound does not inhibit the receptor-ligand interaction. If the ligand does not bind, the method shows that the compound inhibits the receptor-ligand interaction. The method is particularly useful for screening for inhibitors of the interaction between MHC/peptide complex and T cell receptor, MHC/peptide complex and CD8 coreceptor or MHC/peptide complex and CD4 coreceptor.
Screening methods