Evolutionary implications of a third lymphocyte lineage in lampreys

• Type of Material: Article
• Authors: Masa Hirano, Emory University; Peng Guo, Emory University; Nathanael McCurley, Emory University; Michael Schorpp, Max Planck Institute of Immunobiology and Epigenetics; Sabyasachi Das, Emory University; Thomas Boehm, Max Planck Institute of Immunobiology and Epigenetics; Max Dale Cooper, Emory University
• Language: English
• Date: 2013-09-19
• Publisher: Nature Research (part of Springer Nature)
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2013 Macmillan Publishers Limited. All rights reserved
• Final Published Version (URL): http://www.nature.com/nature/journal/v501/n7467/full/nature12467.html
• Title of Journal or Parent Work: Nature
• ISSN: 0028-0836
• Volume: 501
• Issue: 7467
• Start Page: 435
• End Page: 438
• Grant/Funding Information: M.H., P.G., N.M., S.D. and M.D.C. are supported by National Institutes of Health grants (R01AI072435 and R01GM100151) and the Georgia Research Alliance; M.S. and T.B. are supported by the Max Planck Society.
• Research Categories: Health Sciences, Immunology; Health Sciences, Pathology

Abstract

Jawed vertebrates (gnathostomes) and jawless vertebrates (cyclostomes) have different adaptive immune systems1,2. Gnathostomes use T- and B-cell antigen receptors belonging to the immunoglobulin superfamily3,4. 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 cells5–7. Here we define another lineage of T-cell-like lymphocytes that express the recently identified VLRC receptors8,9. 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.