'Big Bang' emergence of the combinatorial immune system

The combinatorial immune response is apparently restricted to jawed vertebrates but identifiable elements of systems for cellular activation and differentiation that may be considered inflammatory mechanisms are widely distributed throughout the Animal Kingdom and even to some degree in plants such as fungi. The combinatorial system is defined by the presence of bona fide immunoglobulins, T-cell receptors, MHC products and enzymes required to allow recombination among gene segments to occur. All of the elements rigorously defining the combinatorial system are found in the most primitive extant jawed vertebrates, the chondrichthyes consisting of sharks and their kin. The chondrichthyes have a surprising degree of diversity in T-cell receptors and immunoglobulin light chains. The heavy chain variable region also displays considerable heterogeneity, although only two types of heavy chains, omega and mu , are present with the mu chain predominating in the serum. Furthermore, the recombination activating gene 1 (RAG1) of sharks has been cloned and completely sequenced with the results indicating a strong conservation of sequence among all jawed vertebrates, but also a recognizable homology to microbial integrases as well as to DNA repair enzymes of yeast.