Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 111, Issue 41, Pages 14828-14833Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1415580111
Keywords
adaptive immunity; molecular evolution; selection; agnatha
Categories
Funding
- Max Planck Society
- European Research Council (ERC) under the European Union's Seventh Framework Programme, ERC [ERC-2012-AdG-323126]
- Intramural Research Program of the National Institutes of Health (NIH), Department of Health and Human Services
- NIH [AI072435, GM100151]
- Georgia Research Alliance
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Lampreys possess two T-like lymphocyte lineages that express either variable lymphocyte receptor (VLR) A or VLRC antigen receptors. VLRA(+) and VLRC+ lymphocytes share many similarities with the two principal T-cell lineages of jawed vertebrates expressing the alpha beta and gamma delta T-cell receptors (TCRs). During the assembly of VLR genes, several types of genomic cassettes are inserted, in step-wise fashion, into incomplete germ-line genes to generate the mature forms of antigen receptor genes. Unexpectedly, the structurally variable components of VLRA and VLRC receptors often possess partially identical sequences; this phenomenon of module sharing between these two VLR isotypes occurs in both lampreys and hagfishes. By contrast, VLRA and VLRC molecules typically do not share their building blocks with the structurally analogous VLRB receptors that are expressed by B-like lymphocytes. Our studies reveal that VLRA and VLRC germ-line genes are situated in close proximity to each other in the lamprey genome and indicate the interspersed arrangement of isotype-specific and shared genomic donor cassettes; these features may facilitate the shared cassette use. The genomic structure of the VLRA/VLRC locus in lampreys is reminiscent of the interspersed nature of the TCRA/TCRD locus in jawed vertebrates that also allows the sharing of some variable gene segments during the recombinatorial assembly of TCR genes.
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