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Sheep (Ovis aries) T cell receptor alpha (TRA) and delta (TRD) genes and genomic organization of the TRA/TRD locus.

Piccinni B, Massari S, Caputi Jambrenghi A, Giannico F, Lefranc MP, Ciccarese S, Antonacci R - BMC Genomics (2015)

Bottom Line: 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.The 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.

View Article: PubMed Central - PubMed

Affiliation: Dipartimento di Scienze e Tecnologie Biologiche ed Ambientali, Universita' del Salento, Lecce, Italy. piccinni.barbara@libero.it.

ABSTRACT

Background: In 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.

Results: The 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.

Conclusions: The 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.

No MeSH data available.


Related in: MedlinePlus

CDR3 nucleotide and predicted AA sequences retrieved from the TRA cDNA clones. CDR3-IMGT sequences are shown from codon 105 (codon after the 2nd-Cys 104 of the V-REGION) to codon 117 (codon before J-PHE 118 of the J-REGION) according to the IMGT unique numbering [27]. Nucleotides of the 3’V-REGION and of the 5’J-REGION are indicated in lower cases. Nucleotides that cannot be attributed to any V or J regions (N-nucleotides) are indicated in capital letters. Numbers in the left and right columns indicate the number of nt that are trimmed from the 3’V-REGION and 5’J-REGION, respectively. The name of the clones and the TRAJ genes is reported
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Fig4: CDR3 nucleotide and predicted AA sequences retrieved from the TRA cDNA clones. CDR3-IMGT sequences are shown from codon 105 (codon after the 2nd-Cys 104 of the V-REGION) to codon 117 (codon before J-PHE 118 of the J-REGION) according to the IMGT unique numbering [27]. Nucleotides of the 3’V-REGION and of the 5’J-REGION are indicated in lower cases. Nucleotides that cannot be attributed to any V or J regions (N-nucleotides) are indicated in capital letters. Numbers in the left and right columns indicate the number of nt that are trimmed from the 3’V-REGION and 5’J-REGION, respectively. The name of the clones and the TRAJ genes is reported

Mentions: For a close inspection of the V-alpha CDR3, the nt sequences from codon 105 to 117 were excised from each cDNA and analysed in detail (Fig. 4). The V-alpha CDR3 loop is heterogeneous for AA composition, especially due to the use of different TRAJ genes involved in the recombination process. The mean length is 11.08 AA (range 7–16 AA) and is approximately the same in spleen (mean 10.5 AA, range 7–13 AA) and thymus (mean 11.7 AA, range 8–16 AA). However, taking into account the TRAV genes, we found a slight increase of the V-alpha CDR3 length in the cDNA expressing TRAV14 genes (mean 12.9 AA, range 11–16 AA) compared to those expressing TRAV21 (mean 11.0 AA, range 8–13 AA) or TRAV25 (mean 9.6 AA, range 7–12 AA), which is probably related to the germline CDR3 lengths of four, three and two AA for TRAV14, TRAV21 and TRAV25, respectively.


Sheep (Ovis aries) T cell receptor alpha (TRA) and delta (TRD) genes and genomic organization of the TRA/TRD locus.

Piccinni B, Massari S, Caputi Jambrenghi A, Giannico F, Lefranc MP, Ciccarese S, Antonacci R - BMC Genomics (2015)

CDR3 nucleotide and predicted AA sequences retrieved from the TRA cDNA clones. CDR3-IMGT sequences are shown from codon 105 (codon after the 2nd-Cys 104 of the V-REGION) to codon 117 (codon before J-PHE 118 of the J-REGION) according to the IMGT unique numbering [27]. Nucleotides of the 3’V-REGION and of the 5’J-REGION are indicated in lower cases. Nucleotides that cannot be attributed to any V or J regions (N-nucleotides) are indicated in capital letters. Numbers in the left and right columns indicate the number of nt that are trimmed from the 3’V-REGION and 5’J-REGION, respectively. The name of the clones and the TRAJ genes is reported
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4574546&req=5

Fig4: CDR3 nucleotide and predicted AA sequences retrieved from the TRA cDNA clones. CDR3-IMGT sequences are shown from codon 105 (codon after the 2nd-Cys 104 of the V-REGION) to codon 117 (codon before J-PHE 118 of the J-REGION) according to the IMGT unique numbering [27]. Nucleotides of the 3’V-REGION and of the 5’J-REGION are indicated in lower cases. Nucleotides that cannot be attributed to any V or J regions (N-nucleotides) are indicated in capital letters. Numbers in the left and right columns indicate the number of nt that are trimmed from the 3’V-REGION and 5’J-REGION, respectively. The name of the clones and the TRAJ genes is reported
Mentions: For a close inspection of the V-alpha CDR3, the nt sequences from codon 105 to 117 were excised from each cDNA and analysed in detail (Fig. 4). The V-alpha CDR3 loop is heterogeneous for AA composition, especially due to the use of different TRAJ genes involved in the recombination process. The mean length is 11.08 AA (range 7–16 AA) and is approximately the same in spleen (mean 10.5 AA, range 7–13 AA) and thymus (mean 11.7 AA, range 8–16 AA). However, taking into account the TRAV genes, we found a slight increase of the V-alpha CDR3 length in the cDNA expressing TRAV14 genes (mean 12.9 AA, range 11–16 AA) compared to those expressing TRAV21 (mean 11.0 AA, range 8–13 AA) or TRAV25 (mean 9.6 AA, range 7–12 AA), which is probably related to the germline CDR3 lengths of four, three and two AA for TRAV14, TRAV21 and TRAV25, respectively.

Bottom Line: 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.The 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.

View Article: PubMed Central - PubMed

Affiliation: Dipartimento di Scienze e Tecnologie Biologiche ed Ambientali, Universita' del Salento, Lecce, Italy. piccinni.barbara@libero.it.

ABSTRACT

Background: In 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.

Results: The 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.

Conclusions: The 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.

No MeSH data available.


Related in: MedlinePlus