Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
Subscribe

Logo for

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}comb.umbi.umd.edu.

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Organization of lamprey variable lymphocyte receptor C locus and repertoire development.
S. Das, M. Hirano, N. Aghaallaei, B. Bajoghli, T. Boehm, and M. D. Cooper (2013)
PNAS 110, 6043-6048
   Abstract »    Full Text »    PDF »
An Evolutionary View of the Mechanism for Immune and Genome Diversity.
L. Kato, A. Stanlie, N. A. Begum, M. Kobayashi, M. Aida, and T. Honjo (2012)
J. Immunol. 188, 3559-3566
   Abstract »    Full Text »    PDF »
Design of a binding scaffold based on variable lymphocyte receptors of jawless vertebrates by module engineering.
S.-C. Lee, K. Park, J. Han, J.-j. Lee, H. J. Kim, S. Hong, W. Heu, Y. J. Kim, J.-S. Ha, S.-G. Lee, et al. (2012)
PNAS 109, 3299-3304
   Abstract »    Full Text »    PDF »
Conservation of the C-type lectin fold for massive sequence variation in a Treponema diversity-generating retroelement.
J. Le Coq and P. Ghosh (2011)
PNAS 108, 14649-14653
   Abstract »    Full Text »    PDF »
Human leucine-rich repeat proteins: a genome-wide bioinformatic categorization and functional analysis in innate immunity.
A. C. Y. Ng, J. M. Eisenberg, R. J. W. Heath, A. Huett, C. M. Robinson, G. J. Nau, and R. J. Xavier (2011)
PNAS 108, 4631-4638
   Abstract »    Full Text »    PDF »
MHC Class I Presentation and Regulation by IFN in Bony Fish Determined by Molecular Analysis of the Class I Locus in Grass Carp.
W. Chen, Z. Jia, T. Zhang, N. Zhang, C. Lin, F. Gao, L. Wang, X. Li, Y. Jiang, X. Li, et al. (2010)
J. Immunol. 185, 2209-2221
   Abstract »    Full Text »    PDF »
Identification of a third variable lymphocyte receptor in the lamprey.
J. Kasamatsu, Y. Sutoh, K. Fugo, N. Otsuka, K. Iwabuchi, and M. Kasahara (2010)
PNAS 107, 14304-14308
   Abstract »    Full Text »    PDF »
Alternative Adaptive Immunity in Jawless Vertebrates.
B. R. Herrin and M. D. Cooper (2010)
J. Immunol. 185, 1367-1374
   Abstract »    Full Text »    PDF »
A structural basis for antigen recognition by the T cell-like lymphocytes of sea lamprey.
L. Deng, C. A. Velikovsky, G. Xu, L. M. Iyer, S. Tasumi, M. C. Kerzic, M. F. Flajnik, L. Aravind, Z. Pancer, and R. A. Mariuzza (2010)
PNAS 107, 13408-13413
   Abstract »    Full Text »    PDF »
Genome Biology of the Cyclostomes and Insights into the Evolutionary Biology of Vertebrate Genomes.
J. J. Smith, N. R. Saha, and C. T. Amemiya (2010)
Integr. Comp. Biol. 50, 130-137
   Abstract »    Full Text »    PDF »
Activation of an Arabidopsis Resistance Protein Is Specified by the in Planta Association of Its Leucine-Rich Repeat Domain with the Cognate Oomycete Effector.
K. V. Krasileva, D. Dahlbeck, and B. J. Staskawicz (2010)
PLANT CELL 22, 2444-2458
   Abstract »    Full Text »    PDF »
High-affinity lamprey VLRA and VLRB monoclonal antibodies.
S. Tasumi, C. A. Velikovsky, G. Xu, S. A. Gai, K. D. Wittrup, M. F. Flajnik, R. A. Mariuzza, and Z. Pancer (2009)
PNAS 106, 12891-12896
   Abstract »    Full Text »    PDF »
Characterization of arrangement and expression of the T cell receptor {gamma} locus in the sandbar shark.
H. Chen, S. Kshirsagar, I. Jensen, K. Lau, R. Covarrubias, S. F. Schluter, and J. J. Marchalonis (2009)
PNAS 106, 8591-8596
   Abstract »    Full Text »    PDF »
The Sea Lamprey Petromyzon marinus: A Model for Evolutionary and Developmental Biology.
N. Nikitina, M. Bronner-Fraser, and T. Sauka-Spengler (2009)
Cold Spring Harb Protoc 2009, pdb.emo113
   Abstract »    Full Text »    PDF »
Antigen Recognition by Variable Lymphocyte Receptors.
B. W. Han, B. R. Herrin, M. D. Cooper, and I. A. Wilson (2008)
Science 321, 1834-1837
   Abstract »    Full Text »    PDF »
Marine Invertebrate Genome Sequences and Our Evolving Understanding of Animal Immunity.
J. P. Rast and C. Messier-Solek (2008)
Biol. Bull. 214, 274-283
   Abstract »    Full Text »    PDF »
Structure and specificity of lamprey monoclonal antibodies.
B. R. Herrin, M. N. Alder, K. H. Roux, C. Sina, G. R. A. Ehrhardt, J. A. Boydston, C. L. Turnbough Jr, and M. D. Cooper (2008)
PNAS 105, 2040-2045
   Abstract »    Full Text »    PDF »
Structural Diversity of the Hagfish Variable Lymphocyte Receptors.
H. M. Kim, S. C. Oh, K. J. Lim, J. Kasamatsu, J. Y. Heo, B. S. Park, H. Lee, O. J. Yoo, M. Kasahara, and J.-O. Lee (2007)
J. Biol. Chem. 282, 6726-6732
   Abstract »    Full Text »    PDF »
Lamprey TLRs with Properties Distinct from Those of the Variable Lymphocyte Receptors.
A. Ishii, A. Matsuo, H. Sawa, T. Tsujita, K. Shida, M. Matsumoto, and T. Seya (2007)
J. Immunol. 178, 397-406
   Abstract »    Full Text »    PDF »
Fc Receptor Homolog 3 Is a Novel Immunoregulatory Marker of Marginal Zone and B1 B Cells.
W.-J. Won, J. B. Foote, M. R. Odom, J. Pan, J. F. Kearney, and R. S. Davis (2006)
J. Immunol. 177, 6815-6823
   Abstract »    Full Text »    PDF »
Genomic Insights into the Immune System of the Sea Urchin.
J. P. Rast, L. C. Smith, M. Loza-Coll, T. Hibino, and G. W. Litman (2006)
Science 314, 952-956
   Abstract »    Full Text »    PDF »
Unexpected diversity displayed in cDNAs expressed by the immune cells of the purple sea urchin, Strongylocentrotus purpuratus.
D. P. Terwilliger, K. M. Buckley, D. Mehta, P. G. Moorjani, and L.C. Smith (2006)
Physiol Genomics 26, 134-144
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882