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Science 310 (5756): 1970-1973

Copyright © 2005 by the American Association for the Advancement of Science

Diversity and Function of Adaptive Immune Receptors in a Jawless Vertebrate

Matthew N. Alder,1 Igor B. Rogozin,2 Lakshminarayan M. Iyer,2 Galina V. Glazko,3 Max D. Cooper,1 Zeev Pancer4*

Abstract: Instead of the immunoglobulin-type antigen receptors of jawed vertebrates, jawless fish have variable lymphocyte receptors (VLRs), which consist of leucine-rich repeat (LRR) modules. Somatic diversification of the VLR gene is shown here to occur through a multistep assembly of LRR modules randomly selected from a large bank of flanking cassettes. The predicted concave surface of the VLR is lined with hypervariable positively selected residues, and computational analysis suggests a repertoire of about 1014 unique receptors. Lamprey immunized with anthrax spores responded with the production of soluble antigen-specific VLRs. These findings reveal that two strikingly different modes of antigen recognition through rearranged lymphocyte receptors have evolved in the jawless and jawed vertebrates.

1 Howard Hughes Medical Institute, Departments of Medicine, Microbiology, Pediatrics, and Pathology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
2 National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA.
3 Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, MO 64110, USA.
4 Center of Marine Biotechnology, University of Maryland Biotechnology Institute, Baltimore, MD 21202, USA.

* To whom correspondence should be addressed. E-mail: pancer{at}

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