Abstract
BackgroundIn mammals, T cells develop along two discrete pathways characterized by expression of either the αβ or the γδ T cell receptors. Human and mouse display a low peripheral blood γδ T cell percentage ("γδ low species") while sheep, bovine and pig accounts for a high proportion of γδ T lymphocytes ("γδ high species"). While the T cell receptor alpha (TRA) and delta (TRD) genes and the genomic organization of the TRA/TRD locus has been determined in human and mouse, this information is still poorly known in artiodactyl species, such as sheep.ResultsThe analysis of the current Ovis aries whole genome assembly, Oar_v3.1, revealed that, as in the other mammalian species, the sheep TRD locus is nested within the TRA locus. In the most 5’ part the TRA/TRD locus contains TRAV genes which are intermingled with TRDV genes, then TRD genes which include seven TRDD, four TRDJ genes, one TRDC and a single TRDV gene with an inverted transcriptional orientation, and finally in the most 3’ part, the TRA locus is completed by 61 TRAJ genes and one TRAC gene.Comparative sequence and analysis and annotation led to the identification of 66 TRAV genes assigned to 34 TRAV subgroups and 25 TRDV genes belonging to the TRDV1 subgroup, while one gene was found for each TRDV2, TRDV3 and TRDV4 subgroups. Multiple duplication events within several TRAV subgroups have generated the sheep TRAV germline repertoire, which is substantially larger than the human one. A significant proportion of these TRAV gene duplications seems to have occurred simultaneously with the amplification of the TRDV1 subgroup genes. This dynamic of expansion has also generated novel multigene subgroups, which are species-specific. Ovis aries TRA and TRD genes identified in this study were assigned IMGT definitive or temporary names and were approved by the IMGT/WHO-IUIS nomenclature committee.The completeness of the genome assembly in the 3' part of the locus has allowed us to interpret rearranged CDR3 of cDNA from both TRA and TRD chain repertoires. The involvement of one up to four TRDD genes into a single transcript makes the potential sheep TRD chain much larger than any known TR chain repertoire.ConclusionsThe sheep genome, as the bovine genome, contains a large and diverse repertoire of TRA and TRD genes when compared to the “γδ T cell low” species genomes. The composition and length of the rearranged CDR3 in TRD V-delta domains influence the three-dimensional configuration of the antigen-combining site thus suggesting that in ruminants, γδ T cells play a more important and specific role in immune recognition.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-015-1790-z) contains supplementary material, which is available to authorized users.
Highlights
In mammals, T cells develop along two discrete pathways characterized by expression of either the αβ or the γδ T cell receptors
The analysis has identified 371 V genes in the T cell receptor alpha (TRA)/TR delta (TRD) locus including 60 belonging to the TRDV1 subgroup, six TRDD, three TRDJ, one TRDC, 62 TRAJ and one TRAC, most of which located within a 3.5 Mb region of chromosome 10
We retrieved a sequence of 1 Mb directly from the chromosome 7 genomic scaffold (NC_019464.1) that comprises the most 5’ variable gene of the TRA locus which is embedded among three olfactory receptor genes in conserved synteny with human and mouse, and the TRAC gene which, by analogy with all mammalian species studied so far, is located at the most 3’ end of the locus
Summary
T cells develop along two discrete pathways characterized by expression of either the αβ or the γδ T cell receptors. While the T cell receptor alpha (TRA) and delta (TRD) genes and the genomic organization of the TRA/TRD locus has been determined in human and mouse, this information is still poorly known in artiodactyl species, such as sheep. T cell populations are characterised by two lymphocyte subsets that express distinct heterodimeric antigenspecific receptors (TRs) formed by alpha and beta chains (αβ T cells) or by gamma and delta chains (γδ T cells). The TR genes are located in four discrete loci on chromosomes: TRA, TRB, TRG and TRD. The whole TRD locus is excised from the genomic sequence when a first TRA V-J rearrangement occurs in the TRA/TRD locus [1]
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