Immunoglobulin superfamily receptors in protochordates: before RAG time.

Urochordates and cephalochordates do not have an adaptive immune system involving the somatic rearrangement of their antigen receptor genes. They do not have antigen-presenting molecules of the major histocompatibility complex (MHC)-linked class I and II types. In the absence of such a system, the status of their genes reflects perhaps a primitive pre-recombination-activating gene (RAG) stage that could suggest the pathway leading to the genesis of the T-cell receptor (TCR) and antibodies. In the genome of Ciona intestinalis, genes that encode molecules with membrane receptor features have been found among many members of the immunoglobulin superfamily (Igsf). They use the domains typical of vertebrate antigen receptors and class I and II: the V, and C1-like domains. These genes belong to two families with recognizable homologs in vertebrates: the junctional adhesion molecule (JAM)/cortical thymocyte marker of Xenopus (CTX) family and the nectin family. The human homologs of these genes segregate in a single unit of four paralogous segments on chromosomes 1q, 3q, 11p, and 21q. These regions contain nowadays several genes involved in the adaptive immune system, and some related members are present in the MHC paralogs as well. They also contain receptor-like genes without homologs in Ciona but with related members in the protostome Drosophila. It looks as if in Ciona one detects what looks like the 'fossil' of one group of genes bound to duplicate and give rise to many crucial elements of the adaptive immune system. The modern homologs of these JAM, CTX, and nectins are all or almost all virus receptors, and the hypothesis is formulated that this property was taken advantage of during evolution to participate in the elaboration of either or both the somatically generated antigen-recognizing receptors and the antigen-presenting molecules.