The human T-cell receptor gamma variable pseudogeneV10 is a distinctive marker of human speciation

Zhang, Xiaomin; Cathala, Guy; Soua, Zohra; Lefranc, Marie‐Paule; Huck, Sylvie

doi:10.1007/bf00587300

Cited by 12 publications

(6 citation statements)

References 42 publications

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“…4). Many TCRγ CDR3 sequences amplified from αβ T cells utilized Vγ10 gene segments, a gene segment predicted to have a non-consensus donor splice site in the first exon, resulting in the absence of splicing of the leader intron and termination of translation of the leader peptide (26, 27). …”

Section: Resultsmentioning

confidence: 99%

Deep Sequencing of the Human TCRγ and TCRβ Repertoires Suggests that TCRβ Rearranges After αβ and γδ T Cell Commitment

et al. 2011

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The two main lineages of T lymphocytes develop from multi potent precursors in the human thymus. The most common type in blood are αβ T cells, which bind to antigenic peptides displayed on the surface of cells by human leukocyte antigen (HLA) molecules. Far less well understood are γδ T cells, which do not bind HLA: peptide complexes and are more prevalent in the gut mucosa. For both lineages, their ability to recognize a diverse array of antigens is mediated by a rearranged Y-like receptor on their surface, the T cell receptor (TCR), composed and of an α and β chain for αβ T cells or a γ and δ chain for γδ T cells. The canonical model for commitment from the precursor to one these two lineages assumes that γ, δ, and β chains rearrange prior to commitment to αβ or γδ T cells. A crucial step towards better understanding the role of γδ T cells is to work out the developmental process. To test the standard model and to understand the γδ TCR repertoire, we use high-throughput sequencing to catalog millions of TCRγ and TCRβ chains from peripheral blood αβ and γδ T cells, from three unrelated individuals. Almost all sampled αβ and γδ T cells have rearranged TCRγ sequences. While sampled αβ T cells have a diverse repertoire of rearranged TCRβ chains, less than 10% of γδ T cells in peripheral blood have a rearranged TCRβ chain. Our data indicate that TCRγ rearranges in all T lymphocytes, consistent with TCRγ rearranging prior to T cell lineage commitment, while rearrangement of the TCRβ locus is restricted, and occurs after T cell precursors commit to the αβ T cell lineage. This result explains the conundrum in T cell leukemia and lymphoma that TCRγ is almost always rearranged and TCRβ is only rearranged in a subset of cancers. As high-throughput sequencing of TCRs is translated into the clinic for monitoring minimal residual for leukemia/lymphoma, our data suggests the sequencing target needs to be TCR γ.

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Section: Resultsmentioning

confidence: 99%

Deep Sequencing of the Human TCRγ and TCRβ Repertoires Suggests that TCRβ Rearranges After αβ and γδ T Cell Commitment

et al. 2011

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“…TRGV9 , expressed in 80–95% of the human peripheral T cells, is the unique member of Subgroup 2. TRGV10 and TRGV11 , the single members of subgroups 3 and 4, respectively, have been found to be rearranged and transcribed, but they are open reading frames (ORFs) that cannot be expressed in a gamma chain, due to a splicing defect of the pre-messenger [ 52 , 53 ]. The potential repertoire consists of four to six functional TRGV genes belonging to two subgroups, five TRGJ and two TRGC genes [ 54 , 55 ].…”

Section: The Homo Sapiens Trg Locusmentioning

confidence: 99%

Evolution of the T-Cell Receptor (TR) Loci in the Adaptive Immune Response: The Tale of the TRG Locus in Mammals

Antonacci

Massari

Linguiti

et al. 2020

Genes

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T lymphocytes are the principal actors of vertebrates’ cell-mediated immunity. Like B cells, they can recognize an unlimited number of foreign molecules through their antigen-specific heterodimer receptors (TRs), which consist of αβ or γδ chains. The diversity of the TRs is mainly due to the unique organization of the genes encoding the α, β, γ, and δ chains. For each chain, multi-gene families are arranged in a TR locus, and their expression is guaranteed by the somatic recombination process. A great plasticity of the gene organization within the TR loci exists among species. Marked structural differences affect the TR γ (TRG) locus. The recent sequencing of multiple whole genome provides an opportunity to examine the TR gene repertoire in a systematic and consistent fashion. In this review, we report the most recent findings on the genomic organization of TRG loci in mammalian species in order to show differences and similarities. The comparison revealed remarkable diversification of both the genomic organization and gene repertoire across species, but also unexpected evolutionary conservation, which highlights the important role of the T cells in the immune response.

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“…Several Vγ pseudogenes are also found in the γ locus in humans and are not used in productively arranged γδ TCRs: Vγ1, Vγ5P, Vγ6, Vγ7 and Vγ10. As discussed in more detail below, these do not all appear to be pseudogenes in other higher primates and at least one (Vγ10) has been found in productively rearranged γ chain transcripts in the chimpanzee [8]. The restricted repertoire of Vδ and Vγ gene segments available for rearrangement has led to speculation that these TCRs recognize conserved self-proteins of low variability [9].…”

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confidence: 99%

Human gamma delta T cells: Evolution and ligand recognition

Adams

Luoma

2015

Cellular Immunology

181

161

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The γδ T cell lineage in humans remains much of an enigma due to the low number of defined antigens, the non-canonical ways in which these cells respond to their environment and difficulty in tracking this population in vivo. In this review, we survey a comparative evolutionary analysis of the primate V, D and J gene segments and contrast these findings with recent progress in T cells in humans. Signatures of both defining antigen recognition by different populations of γδ purifying and diversifying selection at the Vδ and Vγ gene loci are placed into context of Vδ1+ γδ T cell recognition of CD1d presenting different lipids, and Vγ9Vδ2 T cell modulation by pyrophosphate-based phosphoantigens through the butyrophilins BTN3A. From this comparison, it is clear that co-evolution between γδ TCRs and these ligands is likely occurring, but the diversity inherent in these recombined receptors is an important feature in ligand surveillance.

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The human T-cell receptor gamma variable pseudogeneV10 is a distinctive marker of human speciation

Cited by 12 publications

References 42 publications

Deep Sequencing of the Human TCRγ and TCRβ Repertoires Suggests that TCRβ Rearranges After αβ and γδ T Cell Commitment

Deep Sequencing of the Human TCRγ and TCRβ Repertoires Suggests that TCRβ Rearranges After αβ and γδ T Cell Commitment

Evolution of the T-Cell Receptor (TR) Loci in the Adaptive Immune Response: The Tale of the TRG Locus in Mammals

Human gamma delta T cells: Evolution and ligand recognition

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