[Evolutionary development of the immunoglobulins super family]

The origin of the ability of immunoglobulins (Igs) and T-cell receptors (TCRs) to specifically recognize antigens is related to the evolutionary development of proteins of the immunoglobulin superfamily (IgSF). The IgSF proteins are characterized by specific domain organization of molecules and statistically significant homology with known Igs. Four types of Ig domains (V1, V2, C1, and C2), differing from one another both in variations in their spatial organization and in the number of amino acid residues, have been distinguished. Immunoglobulin superfamily comprises Igs; TCRs; class I and II major histocompatibility complex (MHC) molecules; one-domain proteins of thymocytes and T-cells (Thy-1); myelin protein P0; beta 2-microglobulin; two-domain proteins--sponge receptor tyrosine kinase (RTK), sponge adhesive protein (SAP), Drosophila tyrosine-kinase receptor (DTKR), cortical-thymocyte receptors of Xenopus (CTX), human (CTH), etc.; and a large group of adhesins, coreceptors, and Ig receptors with varying number of domains. Evolutionary development of IgSF began with the origination of chaperones, Thy-1, and P0 of prokaryotes and unicellular eukaryotes. Mutations, duplications, and translocations of genes controlling both V and C domains yielded proteins differing in the number and combination of these domains. All IgSF proteins are divided into two groups. The first group includes the proteins with nonrearranging V2 domains and homophilic mode of interaction; the second, the proteins with rearranging V1 domains and heterophilic mode of interaction (Igs, TCRs). The acquisition of the capability of heterophilic antigen-binding mode of interaction was apparently related to the introduction of recombination-activating retroviral genes (RAG1 and RAG2) into the genome of Gnathostomata ancestors.