fester, a Candidate Allorecognition Receptor from a Primitive Chordate

Abstract

Histocompatibility in the primitive chordate, Botryllus schlosseri, is controlled by a single, highly polymorphic locus, the FuHC. By taking a forward genetic approach, we have identified a locus encoded near the FuHC, called fester, which is polymorphic, polygenic, and inherited in distinct haplotypes. Somatic diversification occurs through extensive alternative splicing, with each individual expressing a unique repertoire of splice forms, both membrane bound and potentially secreted, all expressed in tissues intimately associated with histocompatibility. Functional studies, via both siRNA-mediated knockdown and direct blocking by monoclonal antibodies raised against fester, were able to disrupt predicted histocompatibility outcomes. The genetic and somatic diversity, coupled to the expression and functional data, suggests that fester is a receptor involved in histocompatibility.

Histocompatibility as Adaptive Response to Discriminatory Within-Organism Conflict: A Historical Model

“…In botryllid ascidians, histocompatibility functions by means of discriminatory rejection, as evidenced by the occurrence of some fusion before rejection in most species (Saito et al 1994). In the star ascidian Botryllus schlosseri, genetic experiments suggest that the same gene, fester, encodes a receptor that activates both fusion and rejection (Nyholm et al 2006), as assumed here ( fig. 3).…”

Botryllus schlosseri: A model ascidian for the study of asexual reproduction

“…schlosseri, with its capacity for allorecognition of contacting colonies, represents a reference species for studying nonself recognition and the evolution of adaptive vertebrate immunity, strongly supporting the rise of comparative immunology (Oka and Watanabe, 1960;Sabbadin, 1962). The initial hypothesis of the presence of a histocompatibility locus in this species (Sabbadin, 1962;Scofield, 1982a) has recently been confirmed by the isolation and characterization of a protein, which represents the first molecule expressed by a nonvertebrate histocompatibility gene described so far (De Tomaso et al, 2005), as well as a putative receptor involved in allorecognition (Nyholm et al, 2006).…”

“…The locus was named FuHC by Weissmann et al (1990): fusion occurs when at least one allele is shared by the contacting colonies. The high polymorphism at the allorecognition locus is devoted to limiting fusion to genetically related colonies to prevent somatic or germ cell parasitism in the resulting chimeric colonies (Stoner et al, 1999;Laird et al, 2005b;De Tomaso, 2006;Nyholm et al, 2006).…”

“…Embryogenesis is rapid, and larvae for dispersal of new colonies can be obtained within a week from fertilization. In addition, it is already known as a valid model organism for studying natural apoptosis and clearance of effete cells (Burighel and Schiavinato, 1984;Lauzon et al, 1992Lauzon et al, , 1993Lauzon et al, , 2002Cima et al, 2003), allorecognition (Sabbadin, 1962(Sabbadin, , 1982Sabbadin and Astorri, 1988;Ballarin et al, 1995Ballarin et al, , 2002aRinkevich et al, 1998a;Cima et al, 2004a;De Tomaso et al, 2005;Nyholm et al, 2006), immunobiology (Ballarin et al, 1994(Ballarin et al, , 2002bBallarin and Burighel, 2006), and regeneration (Berrill, 1951;Zaniolo and Trentin, 1987;Laird et al, 2005a).…”

Papaver rhoeas S-Determinants and the Signaling Networks They Trigger

“…Self-non-self discrimination and other recognition systems, controlled by a highly polymorphic locus, are found in a wide range of organisms. Allorecognition is widespread and is integral to the animal immune response (Hughes 2002 ), fusion histocompatibility in lower animals (Scofi eld et al 1982 ;De Tomaso et al 2005 ;Nyholm et al 2006 ), vegetative incompatibility in fungi (Glass et al 2000 ), disease resistance in plants (Dangl and Jones 2001 ), and selfincompatibility (SI) systems found in many fl owering plants (Takayama and Isogai 2005 ;Franklin-Tong 2008 ). Parallels between nonanalogous recognition systems were recognized, and their importance appreciated, many years ago (Burnet 1971 ), long before the molecular basis of these systems were elucidated.…”