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Annu Rev Biophys 2013 May 6;42:191-215

Structural Insights into the Evolution of the Adaptive Immune System.

Deng L, Luo M, Velikovsky A, Mariuzza RA


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. Expected final online publication date for the Annual Review of Biophysics Volume 42 is May 06, 2013. Please see http://www.annualreviews.org/catalog/pubdates.aspx for revised estimates.

Category: Journal Article, Review
PubMed ID: #23451889 DOI: 10.1146/annurev-biophys-083012-130422
Includes FDA Authors from Scientific Area(s): Biologics
Entry Created: 2013-03-05 Entry Last Modified: 2013-08-11