The Origin and Early Evolution of Adaptive Immune Systems

  • Masayuki Hirano


Two forms of recombinatorial adaptive immune systems arose in vertebrates about 480 million years ago. The repertoire of immunoglobulin domain-based T and B cell antigen receptors in jawed vertebrates is diversified primarily through the rearrangement of V(D)J (variable, diversity, and/or joining) gene segments and somatic hypermutation, but none of the major recognition elements in jawed vertebrates have been found in jawless vertebrates. Instead, the adaptive immune systems of jawless vertebrates are based on variable lymphocyte receptors (VLRs) that are generated through recombinatorial usage of a large panel of greatly diverse leucine rich repeat sequences. Whereas the emergence of transposon-like, recombination-activating genes (RAGs) contributed uniquely to the origin of the adaptive immune systems in jawed vertebrates, the use of activation-induced cytidine deaminase (AICDA) for receptor diversification is common to both the jawed and jawless vertebrates. Despite these differences in anticipatory receptor structure, the basic design of adaptive immune system featuring two cooperating T and B lymphocyte arms apparently evolved in an ancestor of jawed and jawless vertebrates within the context of established innate immunity and has been sustained due to powerful and durable selection, mostly for pathogen defense commitments.


Adaptive immune system Adaptive immunity Innate immunity Lymphocyte Innate immune cell Vertebrate Jawed vertebrate Jawless vertebrate Invertebrate Variable lymphocyte receptor (VLR) T cell B cell Lamprey Hagfish Gene assembly Evolution 



The author thanks Prof. Edwin L. Cooper for suggestions and critical reading of the manuscript. The author also thanks Dr. Yoichi Sutoh for the figure illustrations. This work is supported by the National Science Foundation.


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© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Emory Vaccine Center and Department of Pathology and Laboratory Medicine, Emory UniversityAtlantaUSA

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