Immunoglobulin superfamily receptors in protochordates: before RAG time

Abstract

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.

Ancestral Organization of the MHC Revealed in the AmphibianXenopus

“…Similarly, the discovery of XMIV genes most related to Ag receptor genes in the Xenopus MHC suggests that they could coevolve with polymorphic class I and/or class II molecules. In addition, based on the fact that class I, class II, and Ag receptor genes all have the specialized Igsf C1-type domain (69,70), it seems likely that the ancestral Ag receptor genes were genetically linked to the MHC-presenting genes. It is possible that the Igsf genes encoded in the Xenopus MHC are relics of such original Ag receptors.…”

Genes “Waiting” for Recruitment by the Adaptive Immune System: The Insights from Amphioxus

“…4. other early chordates (12,55). Their vertebrate counterparts function as the nonimmune or innate immune effector molecules.…”

The Proto-MHC of Placozoans, a Region Specialized in Cellular Stress and Ubiquitination/Proteasome Pathways

“…Class I and class II MHC genes have been suggested to originate from families of molecules present in what is called a "proto-MHC region" for convenience but is involved in innate immunity (12,13). This ancient backbone could be inherited from the invertebrate ancestors of deuterostomians and protostomians (14)(15)(16)(17) (Fig. 1A), from a proto-MHC region.…”