Evolutionary implications of a third lymphocyte lineage in lampreys

Nature. 2013 Sep 19;501(7467):435-8. doi: 10.1038/nature12467. Epub 2013 Aug 11.


Jawed vertebrates (gnathostomes) and jawless vertebrates (cyclostomes) have different adaptive immune systems. Gnathostomes use T- and B-cell antigen receptors belonging to the immunoglobulin superfamily. Cyclostomes, the lampreys and hagfish, instead use leucine-rich repeat proteins to construct variable lymphocyte receptors (VLRs), two types of which, VLRA and VLRB, are reciprocally expressed by lymphocytes resembling gnathostome T and B cells. Here we define another lineage of T-cell-like lymphocytes that express the recently identified VLRC receptors. Both VLRC(+) and VLRA(+) lymphocytes express orthologues of genes that gnathostome γδ and αβ T cells use for their differentiation, undergo VLRC and VLRA assembly and repertoire diversification in the 'thymoid' gill region, and express their VLRs solely as cell-surface proteins. Our findings suggest that the genetic programmes for two primordial T-cell lineages and a prototypic B-cell lineage were already present in the last common vertebrate ancestor approximately 500 million years ago. We propose that functional specialization of distinct T-cell-like lineages was an ancient feature of a primordial immune system.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens / immunology
  • Biological Evolution*
  • Cell Differentiation
  • Cell Lineage*
  • Gene Expression Profiling
  • Lampreys / immunology*
  • Mitogens / immunology
  • Molecular Sequence Data
  • Poly I-C / immunology
  • Proteins / genetics
  • Proteins / immunology
  • Proteins / metabolism
  • T-Lymphocyte Subsets / cytology*
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / metabolism
  • Transcription, Genetic


  • Antigens
  • Mitogens
  • Proteins
  • leucine-rich repeat proteins
  • Poly I-C

Associated data

  • GENBANK/KF385949
  • GENBANK/KF385950
  • GENBANK/KF385951
  • GENBANK/KF385952
  • GENBANK/KF385953
  • GENBANK/KF385954
  • GENBANK/KF385955