Antigen-specific receptors. Generation of the diversity from lamprey to human

In the last century it was established that the diversity of the antigen-recognizing receptors of Band T-lymphocytes and Ig/antibodies in mice and humans is due to the random recombination of DNA segments organized in clusters and located in fetal genome far apart. During somatic rearrangement of genome these segments combine and form functional V-genes, coding antigen-specific receptors. In birds and some other animals the diversity is provided or increased by gene conversion, which leads to the diversification of nucleotide sequences in pre-rearranged functional V-genes. Recently it was shown that the generation of the diversity might be realized by an entirely different way. In most primitive and living now agnathan vertebrates, lamprey and hagfishes, Ig-genes are absent, and somatic diversification of the antigen-specific receptors is due to a stepwise assembly of functional V-genes from separate modules. These modules coding leucine-rich repeats (LRR) adjust to a single (or two) “incomplete” germ-line V-gene and insert into it by gene conversion. LRR modules lodge in so called DNA “cassettes”. The number of LRR in the agnathan genome reaches 2–3 thousands; primary structure of LRR is very variable. The properties of lamprey and hagfish antibodies differ from that of other vertebrates. It is extremely interesting that similar LRR are found in Toll-like receptors of insects, mollusks and even plants, where they provide the resistance to different diseases. The data obtained are very important for the evolutionary immunology. The review deals with the mechanisms of generation of diversity of the antigen-specific receptors in vertebrates, insects, and plants.