Evolutionary implications of a third lymphocyte lineage in lampreys.
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.
Emory Vaccine Center and Department of Pathology and Laboratory Medicine, Emory University, 1462 Clifton Road North-East, Atlanta, Georgia 30322, USA.
Masayuki
M
Hirano
Peng
P
Guo
Nathanael
N
McCurley
Michael
M
Schorpp
Sabyasachi
S
Das
Thomas
T
Boehm
Max D
MD
Cooper
D000818:Animals; D000941:Antigens / Q000276:immunology; D005075:Biological Evolution; D002454:Cell Differentiation; D019070:Cell Lineage; D020869:Gene Expression Profiling; D007798:Lampreys / Q000276:immunology*; D000090263:Leucine-Rich Repeat Proteins; D008934:Mitogens / Q000276:immunology; D008969:Molecular Sequence Data; D011070:Poly I-C / Q000276:immunology; D011506:Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D014158:Transcription, Genetic
D000941:Antigens; D000090263:Leucine-Rich Repeat Proteins; D008934:Mitogens; D011506:Proteins; D011070:Poly I-C