Genotype-specific expression ofuncle festersuggests a role in allorecognition education in a basal chordate

Abstract

AbstractHistocompatibility is the ability to discriminate between self and non-self tissues, and has been described in species throughout the metazoa. Despite its universal presence, histocompatibility genes utilized by different phyla are unique-those found in sponges, cnidarians, ascidians and vertebrates are not orthologous. Thus, the origins of these sophisticated recognition systems, and any potential functional commonalities between them are not understood. A well-studied histocompatibility system exists in the botryllid ascidians, members of the chordate subphylum, Tunicata, and provides an opportunity to do so. Histocompatibility in the botryllids occurs at the tips of an extracorporeal vasculature that come into contact when two individuals grow into proximity. If compatible, the vessels willfuse, forming a parabiosis between the two individuals. If incompatible, the two vessels willreject-an inflammatory reaction that results in melanin scar formation at the point of contact, blocking anastomosis. Compatibility is determined by a single, highly polymorphic locus called thefuhcwith the following rules: individuals that share one or bothfuhcalleles will fuse, while those who share neither will reject. Thefuhclocus encodes multiple proteins with roles in allorecognition, including one calleduncle fester,which is necessary and sufficient to initiate the rejection response. Here we report the existence of genotype-specific expression levels ofuncle fester, differing by up to 8-fold at the mRNA-level, and that these expression levels are constant and maintained for the lifetime of an individual. We also found that these differences had functional consequences: the expression level ofuncle festercorrelated with the speed and severity of the rejection response. These findings support previous conclusions thatuncle festerlevels modulate the rejection response, and may be responsible for controlling the variation observed in the timing and intensity of the reaction. The maintenance of genotype specific expression of uncle fester is also evidence of an education process reminiscent of that which occurs in mammalian Natural Killer (NK) cells. In turn, this suggests that while histocompatibility receptors and ligands evolve via convergent evolution, they may utilize conserved intracellular machinery to interpret binding events at the cell surface.