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Biological Chemistry

Editor-in-Chief: Brüne, Bernhard

Editorial Board: Buchner, Johannes / Lei, Ming / Ludwig, Stephan / Sies, Helmut / Thomas, Douglas D. / Turk, Boris / Wittinghofer, Alfred

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1437-4315
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Volume 391, Issue 7

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

Roy A. Mariuzza
  • University of Maryland Institute for Bioscience and Biotechnology Research, W.M. Keck Laboratory for Structural Biology, Rockville, MD 20850, USA
  • Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD 20742, USA
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ C. Alejandro Velikovsky
  • University of Maryland Institute for Bioscience and Biotechnology Research, W.M. Keck Laboratory for Structural Biology, Rockville, MD 20850, USA
  • Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD 20742, USA
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Lu Deng
  • University of Maryland Institute for Bioscience and Biotechnology Research, W.M. Keck Laboratory for Structural Biology, Rockville, MD 20850, USA
  • Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD 20742, USA
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Gang Xu
  • Center of Marine Biotechnology, University of Maryland Biotechnology Institute, Baltimore, MD 21202, USA
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Zeev Pancer
  • Center of Marine Biotechnology, University of Maryland Biotechnology Institute, Baltimore, MD 21202, USA
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
Published Online: 2010-05-19 | DOI: https://doi.org/10.1515/bc.2010.091

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.

Keywords: adaptive immunity; antibody; complex; evolution; leucine-rich repeat; variable lymphocyte receptor; vertebrates

About the article

Corresponding author


Received: 2010-02-17

Accepted: 2010-04-23

Published Online: 2010-05-19

Published in Print: 2010-07-01


Citation Information: Biological Chemistry, Volume 391, Issue 7, Pages 753–760, ISSN (Online) 1437-4315, ISSN (Print) 1431-6730, DOI: https://doi.org/10.1515/bc.2010.091.

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