Comprehensive genomic analysis of the dromedary T cell receptor gamma (TRG) locus and identification of a functional TRGC5 cassette

Antonacci, Rachele; Linguiti, Giovanna; Burger, Pamela A.; Castelli, Vito; Pala, Angela; Fitak, Robert R.; Massari, Serafina; Ciccarese, Salvatrice

doi:10.1016/j.dci.2020.103614

Cited by 14 publications

(25 citation statements)

References 29 publications

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“…There are three TRGJ genes in the dromedary, as in Bovidae. Finally, the extensive collinearity shared between the entire dromedary TRGC5 cassette sequence and the corresponding cassette of the ovine TRG1 locus further confirmed the “ancient cassette” characteristic of the latter [ 96 ].…”

Section: The Trg Locus In Cetartiodactyla and Carnivora: The “Genementioning

confidence: 94%

“…Only recently, the identification of the 5′ and 3′ boundary genes (defined as IMGT 5′ and 3′ bornes), AMPH and STARD3NL , allowed the complete TRG locus in all its parts to be established in dromedary species [ 96 ]. The dromedary TRG locus is single.…”

Section: The Trg Locus In Cetartiodactyla and Carnivora: The “Genementioning

confidence: 99%

“…The distance between the STARD3NL gene and the last exon of the TRGC2 gene is 8725 bp and in this portion no genes are present. The cassettes are classified as TRGC1, TRGC2, and TRGC5 [ 96 ] ( Table 2 , Supplementary Figure S2B ).…”

Section: The Trg Locus In Cetartiodactyla and Carnivora: The “Genementioning

confidence: 99%

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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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Section: The Trg Locus In Cetartiodactyla and Carnivora: The “Genementioning

confidence: 94%

Section: The Trg Locus In Cetartiodactyla and Carnivora: The “Genementioning

confidence: 99%

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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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“…Despite its functional importance, the immunogenome of camels has received only limited attention with work focusing on cytogenetic mapping in alpaca [14], the characteristics of single-domain heavy-chain antibodies [15] or speci c mechanisms underlying the genetic diversity of T-cell receptors [16][17][18]. Dromedary and two-humped camels are important livestock species, well adapted to harsh conditions and resistant to devastating infections that threaten other livestock species in the same areas, like contagious pleuro-pneumonia [19] or foot-and-mouth disease in dromedaries [20].…”

Section: Discussionmentioning

confidence: 99%

Nucleotide diversity of functionally different groups of immune response genes in Old World camels based on newly annotated and reference-guided assemblies

Lado¹,

Elbers²,

Rogers

et al. 2020

Preprint

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Background Immune-response (IR) genes have an important role in the defense against highly variable pathogens, and therefore, genetic diversity in these genomic regions is essential for species’ survival and adaptation. Although current genome assemblies from Old World camelids are very useful for investigating genome-wide diversity, demography and population structure, they have inconsistencies and gaps that limit analyses at local genomic scales. Improved and more accurate genome assemblies and annotations are needed to study complex genomic regions like adaptive and innate IR genes. Results In this work, we improved the genome assemblies in the three Old World camel species – domestic dromedary and Bactrian camel, and the two-humped wild camel – via different computational methods. The newly annotated dromedary genome assembly CamDro3 served as reference to scaffold the NCBI RefSeq genomes of domestic Bactrian and wild camels. These upgraded assemblies were then used to assess nucleotide diversity of IR genes within and between species, and to compare the diversity found in immune genes and the rest of the genes in the genome. We detected differences in the nucleotide diversity among the three Old World camelid species and between IR gene groups, i.e., innate versus adaptive. Among the three species, domestic Bactrian camels showed the highest mean nucleotide diversity. Among the functionally different IR gene groups, the highest mean nucleotide diversity was observed in the major histocompatibility complex. Conclusions The new camel genome assemblies were greatly improved in terms of contiguity and increased size with fewer scaffolds, which is of general value for the scientific community. This allowed us to perform in-depth studies on genetic diversity in immunity-related regions of the genome. Our results suggest that differences of diversity across classes of genes appear compatible with being caused by a combination of population history coupled with possible distinct exposures to pathogens and consequent different selective pressures.

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“…Human TCR δ-chains contain up to three D gene-encoded segments, which increases not only the variability of CDR3δ lengths but also massively impacts sequence diversity, since up to four sites of recombination can be incorporated in a CDR3 of a TCR δ-chain [ 2 , 4 ]. For very few species, somatic hypermutations have been described for TCR loci such as the TRA , TRG, and TRD of nurse sharks [ 5 , 6 ] and TRG and TRD of dromedary [ 7 , 8 ]. Many Gnathostomata, but not mice and humans, possess additional types of RAG-recombined Ig domain-containing antigen receptors that can be considered functional analogues to TCRs or BCRs, respectively [ 4 , 9 ].…”

Section: T Cell Receptors and Antigensmentioning

confidence: 99%

An Update on the Molecular Basis of Phosphoantigen Recognition by Vγ9Vδ2 T Cells

Herrmann

Fichtner

Karunakaran

2020

Cells

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About 1–5% of human blood T cells are Vγ9Vδ2 T cells. Their hallmark is the expression of T cell antigen receptors (TCR) whose γ-chains contain a rearrangement of Vγ9 with JP (TRGV9JP or Vγ2Jγ1.2) and are paired with Vδ2 (TRDV2)-containing δ-chains. These TCRs respond to phosphoantigens (PAg) such as (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMBPP), which is found in many pathogens, and isopentenyl pyrophosphate (IPP), which accumulates in certain tumors or cells treated with aminobisphosphonates such as zoledronate. Until recently, these cells were believed to be restricted to primates, while no such cells are found in rodents. The identification of three genes pivotal for PAg recognition encoding for Vγ9, Vδ2, and butyrophilin (BTN) 3 in various non-primate species identified candidate species possessing PAg-reactive Vγ9Vδ2 T cells. Here, we review the current knowledge of the molecular basis of PAg recognition. This not only includes human Vγ9Vδ2 T cells and the recent discovery of BTN2A1 as Vγ9-binding protein mandatory for the PAg response but also insights gained from the identification of functional PAg-reactive Vγ9Vδ2 T cells and BTN3 in the alpaca and phylogenetic comparisons. Finally, we discuss models of the molecular basis of PAg recognition and implications for the development of transgenic mouse models for PAg-reactive Vγ9Vδ2 T cells.

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Comprehensive genomic analysis of the dromedary T cell receptor gamma (TRG) locus and identification of a functional TRGC5 cassette

Cited by 14 publications

References 29 publications

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

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

Nucleotide diversity of functionally different groups of immune response genes in Old World camels based on newly annotated and reference-guided assemblies

An Update on the Molecular Basis of Phosphoantigen Recognition by Vγ9Vδ2 T Cells

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