The immunoglobulin fold predates the evolution of vertebrates. Genomes of invertebrate organisms encode numerous molecules that belong to two families with homologs in vertebrates: the JAM/cortical thymocyte marker of Xenopus (CTX) family and the nectin family [17] . Vertebrate counterparts of these genes are found in discrete blocks, and many are now diversified to encode molecules that function in adaptive immunity, including CD3 and SLAM [17] . Invertebrates do not encode recombination-activating genes (RAGs) and generally display only limited antigen-specific immunity. Therefore, the core structural element of adaptive immunity, the immunoglobulin fold, evolved prior to a mechanism to generate a highly diversified antigen-specific repertoire.