Variable lymphocyte receptor F is generated via somatic diversification and expressed by lamprey T-like cellsShow others and affiliations
2025 (English)In: Nature Communications, E-ISSN 2041-1723, Vol. 16, no 1, article id 6503Article in journal (Refereed) Published
Abstract [en]
All extant jawless vertebrates (lampreys and hagfishes) possess a unique adaptive immune system characterized by highly variable lymphocyte receptors (VLR) that are assembled in developing lymphocytes using leucine-rich-repeat donor cassettes. Five VLR types have been identified in lampreys: VLRA, VLRB, VLRC, VLRD, and VLRE. VLRB-expressing lymphocytes are functional analogs to B cells, whereas VLRA, VLRC, VLRD, and VLRE-expressing lymphocytes are more akin to T cells of jawed vertebrates. Here we define an additional VLR, designated VLRF. VLRF is phylogenetically closest to VLRA, with which it likely shares a common ancestral gene of at least 250 million years in the past. VLR assembly analyses show that VLRA, VLRC, VLRD, VLRE, and VLRF share donor cassettes through long-range intra- and inter-chromosomal interactions, whereas VLRB utilizes a distinct, dedicated cassette set. The pattern of gene expression, donor cassette usage, and distinctive amino acid composition in the C-terminal stalk suggest that VLRF⁺ lymphocytes may represent an additional T-like sub-lineage, adding further complexity to the VLR-based adaptive immune system.
Place, publisher, year, edition, pages
Springer Nature, 2025. Vol. 16, no 1, article id 6503
National Category
Medical Biotechnology (Focus on Cell Biology, (incl. Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
URN: urn:nbn:se:umu:diva-242344DOI: 10.1038/s41467-025-61187-1Scopus ID: 2-s2.0-105010607480OAI: oai:DiVA.org:umu-242344DiVA, id: diva2:1985619
Funder
NIH (National Institutes of Health), R01AI072435; R35GM122591; GM1088382025-07-252025-07-252025-07-25Bibliographically approved