The Evolutionary Origins of the Adaptive Immune System of Jawed Vertebrates

This chapter focuses on how the essential components of the adaptive immune system-Ab, TcR, and MHC molecules-arose and began to interact. The major histocompatibility complex (MHC) molecules are loaded with their antigens by sophisticated pathways composed of various kinds of molecules, some of which are encoded by genes located in the MHC. In all jawed vertebrates examined thus far, the essential elements of the adaptive immune system are present. Despite years of functional experiments with invertebrates pointing to recognition of allo- and xenoantigens, none of the essential genetic components of the adaptive immune system in the jawed vertebrates were found in the first complete genomic sequences of invertebrates: an insect (the fruit fly Drosophila melanogaster) and a nematode worm (Caenorhabditis elegans). Therefore, the notion that invertebrates lack an adaptive immune system was strengthened, and the question became how invertebrates managed to survive without a system that is essential to jawed vertebrates. A key concept that has relevance no matter what the defense system might be is that pathogens that overcome all of their hosts may face a bleak evolutionary future, and so, in general, the virulence of pathogens is constrained and guided by the particular defenses that their host(s) evolve. Although there is little scope to observe the evolution of the immune system through fossils, it seems likely that the adaptive immune system of the jawed vertebrates also evolved in steps, none of which are separated between those organisms still living.