50 million years of chordate evolution: seeking the origins of adaptive immunity.

Agnathans, the most primitive chordates, are poised at a fascinating point in evolution. In the 50 million years between agnathan and chondrichthian divergence, something mysterious, even miraculous occurred: the adaptive immune system evolved. A complex, interdependent system of checks and balances in which fragments of both intracellular and extracellularly derived foreign molecules (antigens) are presented in the clutch of MHC cell surface molecules to 1016 possible different lymphocyte receptors arose seemingly overnight in evolutionary time. Moreover, the system that evolved before the divergence of jawed fish was so successful that the basic paradigm remained throughout the radiation of subsequent vertebrate lineages.

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