The present invention relates to novel screening methods for identifying agonists and antagonists of toll-like receptor (TLR) 7, TLR8 or TLR9. Methods are disclosed for identifying agonists and antagonists of TLR7, TLR8 or TLR9 using mutant TLR proteins containing deletions in one or more extracellular leucine rich regions (LRRs). Such agonists and antagonists have utility in the prevention, treatment and/or cure of various diseases and conditions, including cancer, virus infection, allergy, asthma, and chronic obstructive pulmonary disease (COPD).