Structural insights into the evolution of the adaptive immune system: the variable lymphocyte receptors of jawless vertebrates.

Printer-friendly versionPrinter-friendly versionPDF versionPDF version
TitleStructural insights into the evolution of the adaptive immune system: the variable lymphocyte receptors of jawless vertebrates.
Publication TypeJournal Article
Year of Publication2010
AuthorsMariuzza, RA, Velikovsky, CA, Deng, L, Xu, G, Pancer, Z
JournalBiol Chem
Volume391
Issue7
Pagination753-60
Date Published2010 Jul
ISSN1437-4315
KeywordsAdaptive Immunity, Animals, Evolution, Molecular, Immune System, Jaw, Lymphocytes, Protein Conformation, Receptors, Immunologic, Vertebrates
Abstract

Adaptive immunity in jawless vertebrates is mediated by antigen receptors that are fundamentally different from those of jawed vertebrates. Whereas antibodies and T cell receptors (TCRs) are composed of immunoglobulin (Ig) domains, the variable lymphocyte receptors (VLRs) of jawless fish consist of leucine-rich repeat (LRR) modules. As with antibodies and TCRs, VLRs are assembled by DNA recombination in a process that generates a vast repertoire of receptors. VLRs recognize as diverse an array of particulate and soluble antigens as Ig-based antibodies, and do so with similar affinity and specificity. X-ray crystallographic studies of VLRs in complex with protein and carbohydrate antigens have shown that these LRR-based receptors use nearly all their concave surface to bind ligands, in addition to a highly variable loop in their C-terminal LRR capping module. This structural information, combined with a comprehensive analysis of VLR sequences, has revealed an almost perfect match between antigen-contacting positions and positions with highest sequence diversity. The independent evolution approximately 500 million years ago of LRR-based and Ig-based receptors of comparable diversity and antigen-binding properties provides evidence for the survival value of adaptive immunity in vertebrates.

DOI10.1515/BC.2010.091
Alternate JournalBiol. Chem.
PubMed ID20482318
Grant ListAI036900 / AI / NIAID NIH HHS / United States
AI083892 / AI / NIAID NIH HHS / United States