Structural insights into the evolution of the adaptive immune system.

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TitleStructural insights into the evolution of the adaptive immune system.
Publication TypeJournal Article
Year of Publication2013
AuthorsDeng, L, Luo, M, Velikovsky, CA, Mariuzza, RA
JournalAnnu Rev Biophys
Date Published05/09/2013
KeywordsAdaptive Immunity, Animals, Biological Evolution, Lymphocytes, Receptors, Antigen, Receptors, Immunologic, Vertebrates

The adaptive immune system, which is based on highly diverse antigen receptors that are generated by somatic recombination, arose approximately 500 Mya at the dawn of vertebrate evolution. In jawed vertebrates, adaptive immunity is mediated by antibodies and T cell receptors (TCRs), which are composed of immunoglobulin (Ig) domains containing hypervariable loops that bind antigen. In striking contrast, the adaptive immune receptors of jawless vertebrates, termed variable lymphocyte receptors (VLRs), are constructed from leucine-rich repeat (LRR) modules. Structural studies of VLRs have shown that these LRR-based receptors bind antigens though their concave surface, in addition to a unique hypervariable loop in the C-terminal LRR capping module. These studies have revealed a remarkable example of convergent evolution in which jawless vertebrates adopted the LRR scaffold to recognize as broad a spectrum of antigens as the Ig-based antibodies and TCRs of jawed vertebrates, with altogether comparable affinity and specificity.

Alternate JournalAnnu Rev Biophys
PubMed ID23451889
Grant ListAI036900 / AI / NIAID NIH HHS / United States
AI073654 / AI / NIAID NIH HHS / United States