Résumé : Allorecognition, the ability to discriminate between self and nonself, is ubiquitous among colonial metazoans and widespread among aclonal taxa [1-3]. Genetic models for the study of allorecognition have been developed in the jawed vertebrates [4], invertebrate chordate Botryllus [5, 6], and cnidarian Hydractinia [7]. In Botryllus, two genes contribute to the histocompatibility response, FuHC [5, 8] and fester [6]. In the cnidarian Hydractinia, one of the two known allorecognition loci, alr2, has been isolated [7], and a second linked locus, alr1, has been mapped to the same chromosomal region, called the allorecognition complex (ARC) [9, 10]. Here we isolate alr1 by positional cloning and report it to encode a transmembrane receptor protein with two hypervariable extracellular regions similar to immunoglobulin (Ig)-like domains. Variation in the extracellular domain largely predicts fusibility within and between laboratory strains and wild-type isolates. alr1 was found embedded in a family of immunoglobulin superfamily (IgSF)-like genes, thus establishing that the ARC histocompatibility complex is an invertebrate IgSF-like gene complex. © 2010 Elsevier Ltd. All rights reserved.