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<p>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. <i>VLRF</i> is phylogenetically closest to <i>VLRA</i>, with which it likely shares a common ancestral gene of at least 250 million years in the past. <i>VLR</i> assembly analyses show that <i>VLRA</i>, <i>VLRC</i>, <i>VLRD</i>, <i>VLRE</i>, and <i>VLRF</i> share donor cassettes through long-range intra- and inter-chromosomal interactions, whereas <i>VLRB</i> 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.</p>

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Variable lymphocyte receptor F is generated via somatic diversification and expressed by lamprey T-like cells

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年7月15日

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  • Sabyasachi Das,
  • Francisco Fontenla-Iglesias,
  • Masayuki Hirano,
  • Ryo Morimoto,
  • Byron B. Au-Yeung,
  • Yashuo Wang,
  • Weiming Li,
  • Thomas Boehm,
  • Jonathan P. Rast,
  • Max D. Cooper

摘要

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.