The Structure of Vertebrate Antigen Receptor Repertoires: An Evolutionary Perspective

In vertebrate adaptive immune systems, somatically diversified antigen receptors assume a central role in self/nonself discrimination. Attesting to the presence of a unique but unknown selective environment at early stages of vertebrate evolution, this facility emerged twice, in the ancestors of jawless and jawed vertebrates. Thus, the molecular structure of incomplete antigen receptor genes and their mode of assembly into functional genes are different in the two sister groups of vertebrates. It appears that adaptive immunity evolved in steps, trading immunologically favorable diversity of antigen receptor repertoires against the inherent risks of potentially destructive self recognition. Initially, the associated quality control mechanisms were largely cell-autonomous and grounded in the evolutionarily selected sequence composition of individual components available for assembly. At later stages, diversity increased in lock-step with emerging cell-nonautonomous quality control strategies: primary lymphoid organs spatially and temporally coupled repertoire development and assessment for self reactivity; regulatory cell types emerged to keep self reactive clones in check in the periphery. In this review, we discuss how comparative studies of vertebrate species situated at key positions in the phylogenetic tree have revealed traces of the evolutionary past of adaptive immune systems.