A Hypervariable Invertebrate Allodeterminant

Abstract

Summary Colonial marine invertebrates, such as sponges, corals, bryozoans, and ascidians, often live in densely-populated communities where they encounter other members of their species as they grow over their substratum. Such encounters typically lead to a natural histocompatibility response in which colonies either fuse to become a single, chimeric colony or reject and aggressively compete for space. These allorecognition phenomena mediate intraspecific competition [1–3], support allotypic diversity [4], control the level at which selection acts [5–8], and resemble allogeneic interactions in pregnancy and transplantation [9–12]. Despite the ubiquity of allorecognition in colonial phyla, however, its molecular basis has not been identified beyond what is currently known about histocompatibility in vertebrates and protochordates. We positionally cloned an allorecognition gene using inbred strains of the cnidarian, Hydractinia symbiolongicarpus, which is a model system for the study of invertebrate allorecognition. The gene identified encodes a putative transmembrane receptor expressed in all tissues capable of allorecognition that is highly polymorphic and predicts allorecognition responses in laboratory and field-derived strains. This study reveals that a previously undescribed hypervariable molecule bearing three extracellular domains with greatest sequence similarity to the immunoglobulin superfamily is an allodeterminant in a lower metazoan.

An Innate Response to Allogeneic Nonself Mediated by Monocytes

“…Specific allorecognition systems that predate the emergence of lymphocytes and the MHC have been identified in colonial marine invertebrates (26,47). These systems prevent fusion between genetically disparate members of the same species and thus, serve as safeguards against stem cell and germline parasitism (25,28).…”

“…The ubiquity of rejection responses, particularly among colonial marine invertebrates, has led to the proposal that allorecognition evolved before the emergence of vertebrate adaptive immune systems, characterized by polymorphic MHC molecules and re-arranging lymphocyte receptors, and that it serves to protect the organism against stem cell parasitism (22)(23)(24)(25). The recent identification of specific allorecognition systems in two colonial marine organisms, Botryllus and Hydractinia (26,27), and the characterization of their role in preventing stem cell chimerism (28,29), have confirmed these earlier suspicions. To investigate whether the mammalian immune system mounts an alloimmune response independent of lymphocytes, we studied the cutaneous reaction of RAG Ϫ/Ϫ mice to cells transplanted from allogeneic donors.…”

Hydractinia, a pioneering model for stem cell biology and reprogramming somatic cells to pluripotency

“…3 D-1). Fusion can also occur between allogeneic tissues resulting in a common chimeric colony, mostly restricted to close kin (Hauenschild, 1954(Hauenschild, , 1956, which share at least one alr locus (Nicotra et al, 2009;Rosa et al, 2010;Rosengarten et al, 2011;Rosengarten and Nicotra, 2011).…”

“…Although first pioneering genetic analyses date back several decades (Hauenschild, 1954(Hauenschild, , 1956 in H. echinata) only extensive positional cloning of two allorecognition loci alr1 and alr2 in H. symbiolongicarpus (Mokady and Buss 1996;Cadavid et al, 2004;Schwarz et al, 2007;Nicotra et al, 2009;Rosa et al, 2010;Rosengarten et al, 2011;Rosengarten and Nicotra, 2011) eventually provided evidence for the involvement of molecules belonging to the immunoglobulin superfamily. In 2009 a first gene was identified that encodes a putative transmembrane receptor expressed in all tissues capable of allorecognition.…”

“…In 2009 a first gene was identified that encodes a putative transmembrane receptor expressed in all tissues capable of allorecognition. It is highly polymorphic and gives rise to a previously undescribed hypervariable protein bearing three extracellular domains with significant sequence similarity to the immunoglobulin superfamily, which is known to encode allodeterminants in other animals (Nicotra et al, 2009). However, like in the MHC-mediated allorecognition system of vertebrates, the individual identity is not encoded by a single polymorphic gene but by clusters of paralogous alr genes (Rosengarten et al, 2011;Rosengarten and Nicotra, 2011).…”