Genetic and functional diversity of allorecognition receptors in the urochordate, Botryllus schlosseri

Allorecognition in Botryllus schlosseri is controlled by a highly polymorphic locus (the fuhc), and functionally similar to missing-self recognition utilized by Natural Killer cells-compatibility is determined by sharing a self-allele, and integration of activating and inhibitory signals determines outcome. We had found these signals were generated by two fuhc-encoded receptors, called fester and uncle fester. Here we show that fester genes are members of an extended family consisting of >37 loci, and co-expressed with an even more diverse gene family-the fester co-receptors (FcoR). The FcoRs are membrane proteins related to fester, but include conserved tyrosine motifs, including ITIMs and hemITAMs. Both genes are encoded in highly polymorphic haplotypes on multiple chromosomes, revealing an unparalleled level of diversity of innate receptors. Our results also suggest that ITAM/ITIM signal integration is a deeply conserved mechanism that has allowed convergent evolution of innate and adaptive cell-based recognition systems.