(A) Alignment of the amino acid sequence of the cytoplasmic domains of the IL-1R and the Toll/IL-1R–like family members: Drosophila wheeler and Toll, human Toll, TIL, TIL3, and TIL4. Alignments were performed using the Clustal algorithm49 and Boxshade (http://ulrec3.unil.ch/software/BOX_faq.html). Sequence identity (black) or similarity (gray) between at least 40% of the sequence members are shaded. Inactivating dToll mutations are marked with an asterisk (*).13 Critical amino acid residues for IL-1R activation of IL-2 are denoted by a solid circle (•),12,42 for IL-1R activation of IL-8 by a cross (+),45 and IL-1R activation of NF-κB by a box (□).43 (B) Alignment of the extracellular LRR terminal-flanking sequences of the LRR proteins TIL3, TIL4, TIL, hToll, dToll, human platelet glycoprotein 1b-α (Gp1b-α) and 1b-β (gp1b-β),27,47 platelet glycoprotein IX (gpIX),28 leucine-rich glycoprotein (LRG),29and the oncofetal antigen 5T4 (ofg-5T4).30 The extracellular region of dToll contains two cysteine-rich LRR domains (dToll #1 and dToll#2). Sequence identity (black) or similarity (gray) between at least 40% of the sequence members are shaded. The mutations responsible for the dominant, constitutively active dToll proteins are denoted by asterisk (*) and are located in the second dToll terminal repeat.13