Journal
NATURE
Volume 501, Issue 7467, Pages 435-+Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nature12467
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Funding
- National Institutes of Health [R01AI072435, R01GM100151]
- Georgia Research Alliance
- Max Planck Society
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Jawed vertebrates (gnathostomes) and jawless vertebrates (cyclostomes) have different adaptive immune systems(1,2). Gnathostomes use T- and B-cell antigen receptors belonging to the immunoglobulin superfamily(3,4). 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(5-7). Here we define another lineage of T-cell-like lymphocytes that express the recently identified VLRC receptors(8,9). Both VLRC+ and VLRA(+) lymphocytes express orthologues of genes that gnathostome gamma delta and alpha beta 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.
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