ArticleProceedings of the National Academy of Sciences of the United States of America2014
Selection of the lamprey VLRC antigen receptor repertoire.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 36 citations in OpenAlex.
- Evolutionary Comparative Analyses of DNA-Editing Enzymes of the Immune System: From 5-Dimensional Description of Protein Structures to Immunological Insights and Applications to Protein Engineering.Frontiers in immunology · 2021Pooled it
- The Structure of Vertebrate Antigen Receptor Repertoires: An Evolutionary Perspective.Immunological reviews · 2026Review
- Multiple evolutionary routes to immune diversification across animals.International immunology · 2026Review
- LampreyProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Variable lymphocyte receptor F is generated via somatic diversification and expressed by lamprey T-like cells.Nature communications · 2025Article
- Article
- Understanding vertebrate immunity through comparative immunology.Nature reviews. Immunology · 2025Review
- γδ T, NKT, and MAIT Cells During Evolution: Redundancy or Specialized Functions?Journal of immunology (Baltimore, Md. : 1950) · 2022Review
- Review
- On the relationship between extant innate immune receptors and the evolutionary origins of jawed vertebrate adaptive immunity.Immunogenetics · 2022Review
- Review
- The immune system of jawless vertebrates: insights into the prototype of the adaptive immune system.Immunogenetics · 2021Review
- Evolution of thymopoietic microenvironments.Open biology · 2021Review
- Speculations on the evolution of humoral adaptive immunity.Immunology and cell biology · 2020Review
- Zebrafish and Medaka: Two Teleost Models of T-Cell and Thymic Development.International journal of molecular sciences · 2019Review
- Expansions, diversification, and interindividual copy number variations of AID/APOBEC family cytidine deaminase genes in lampreys.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Structural Insights into VLR Fine Specificity for Blood Group Carbohydrates.Structure (London, England : 1993) · 2017Article
- Biochemical Regulatory Features of Activation-Induced Cytidine Deaminase Remain Conserved from Lampreys to Humans.Molecular and cellular biology · 2017Article
- A Novel Vav3 Homolog Identified in Lamprey, Lampetra japonica, with Roles in Lipopolysaccharide-Mediated Immune Response.International journal of molecular sciences · 2017Article
- Structure of a variable lymphocyte receptor-like protein from the amphioxus Branchiostoma floridae.Scientific reports · 2016Article
Corrections and comments
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Authors and funding
10 authors at 6 institutions in 3 countries.
Funding
Abstract
The alternative adaptive immune system of jawless vertebrates is based on different isotypes of variable lymphocyte receptors (VLRs) that are composed of leucine-rich repeats (LRRs) and expressed by distinct B- and T-like lymphocyte lineages. VLRB is expressed by B-like cells, whereas VLRA and VLRC are expressed by two T-like lineages that develop in the thymoid, a thymus-like structure in lamprey larvae. In each case, stepwise combinatorial insertions of different types of short donor LRR cassettes into incomplete germ-line genes are required to generate functional VLR gene assemblies. It is unknown, however, whether the diverse repertoires of VLRs that are expressed by peripheral blood lymphocytes are shaped by selection after their assembly. Here, we identify signatures of selection in the peripheral repertoire of VLRC antigen receptors that are clonally expressed by one of the T-like cell types in lampreys. Selection strongly favors VLRC molecules containing four internal variable leucine-rich repeat (LRRV) modules, although VLRC assemblies encoding five internal modules are initially equally frequent. In addition to the length selection, VLRC molecules in VLRC(+) peripheral lymphocytes exhibit a distinct pattern of high entropy sites in the N-terminal LRR1 module, which is inserted next to the germ-line-encoded LRRNT module. This is evident in comparisons to VLRC gene assemblies found in the thymoid and to VLRC gene assemblies found in some VLRA(+) cells. Our findings are the first indication to our knowledge that selection operates on a VLR repertoire and provide a framework to establish the mechanism by which this selection occurs during development of the VLRC(+) lymphocyte lineage.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.