The genomic organisation of the tra/trd locus validates the peculiar characteristics of dromedary δ-chain expression

The role of γδ T cells in vertebrate immunity is still an unsolved puzzle. Species such as humans and mice display a low percentage of these T lymphocytes (i.e., “γδ low species”) with a restricted diversity of γδ T cell receptors (TR). Conversely, artiodactyl species (i.e., “γδ high species”) account for a high proportion of γδ T cells with large γ and δ chain repertoires. The genomic organisation of the TR γ (TRG) and δ (TRD) loci has been determined in sheep and cattle, noting that a wide number of germline genes that encode for γ and δ chains characterise their genomes. Taking advantage of the current improved version of the genome assembly, we have investigated the genomic structure and gene content of the dromedary TRD locus, which, as in the other mammalian species, is nested within the TR α (TRA) genes. The most remarkable finding was the identification of a very limited number of variable germline genes (TRDV) compared to sheep and cattle, which supports our previous expression analyses for which the somatic hypermutation mechanism is able to enlarge and diversify the primary repertoire of dromedary δ chains. Furthermore, the comparison between genomic and expressed sequences reveals that D genes, up to four incorporated in a transcript, greatly contribute to the increased diversity of the dromedary δ chain antigen binding-site

New insight into the genomic structure of dog T cell receptor beta (TRB) locus inferred from expression analysis

Here is an updated report on the genomic organization of T cell receptor beta (TRB) locus in the domestic dog (Canis lupus familiaris) as inferred from comparative genomics and expression analysis. The most interesting results we found were a second TRBD–J–C cluster, which is absent from the reference genome sequence, and the annotation of two additional TRBV genes. In dogs, TRB locus consists of a library of 37 TRBV genes positioned at the 50 end of two in tandem aligned D–J–C gene clusters, each composed of a single TRBD, 6 TRBJ and one TRBC genes, followed by a single TRBV gene with an inverted transcriptional orientation. The TRB genes are distributed in less than 300 kb, making the canine locus, one of the smaller mammalian TRB locus studied so far. The small size may be ascribed to reduced gene duplication occurrences and a lower density of total interspersed repeats compared to humans and mice. Despite the low TRBV gene content, a large and diversified beta chain repertoire is displayed in the dog peripheral blood. A full usage of TRBV and TRBJ genes, including pseudogenes, and a high level of allelic polymorphism contribute to generate diversity. Finally, this study suggests that the overall TRB locus organization is evolutionarily conserved supporting the dog as a highly suited model system for immune development and diseases

Evolution of the T-cell receptor (TR) Loci in the adaptive immune response: The tale of the TRG locus in mammals

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

The Organization of the Pig T-Cell Receptor γ (TRG) Locus Provides Insights into the Evolutionary Patterns of the TRG Genes across Cetartiodactyla

The domestic pig (Sus scrofa) is a species representative of the Suina, one of the four suborders within Cetartiodactyla. In this paper, we reported our analysis of the pig TRG locus in comparison with the loci of species representative of the Ruminantia, Tylopoda, and Cetacea suborders. The pig TRG genomic structure reiterates the peculiarity of the organization of Cetartiodactyla loci in TRGC "cassettes", each containing the basic V-J-J-C unit. Eighteen genes arranged in four TRGC cassettes, form the pig TRG locus. All the functional TRG genes were expressed, and the TRGV genes preferentially rearrange with the TRGJ genes within their own cassette, which correlates the diversity of the γ-chain repertoire with the number of cassettes. Among them, the TRGC5, located at the 5' end of the locus, is the only cassette that retains a marked homology with the corresponding TRGC cassettes of all the analyzed species. The preservation of the TRGC5 cassette for such a long evolutionary time presumes a highly specialized function of its genes, which could be essential for the survival of species. Therefore, the maintenance of this cassette in pigs confirms that it is the most evolutionarily ancient within Cetartiodactyla, and it has undergone a process of duplication to give rise to the other TRGC cassettes in the different artiodactyl species in a lineage-specific manner

The t cell receptor (Trb) locus in tursiops truncatus: From sequence to structure of the alpha/beta heterodimer in the human/dolphin comparison

The bottlenose dolphin (Tursiops truncatus) belongs to the Cetartiodactyla and, similarly to other cetaceans, represents the most successful mammalian colonization of the aquatic envi-ronment. Here we report a genomic, evolutionary, and expression study of T. truncatus T cell receptor beta (TRB) genes. Although the organization of the dolphin TRB locus is similar to that of the other artiodactyl species, with three in tandem D-J-C clusters located at its 3’ end, its unique-ness is given by the reduction of the total length due essentially to the absence of duplications and to the deletions that have drastically reduced the number of the germline TRBV genes. We have analyzed the relevant mature transcripts from two subjects. The simultaneous availability of rear-ranged T cell receptor α (TRA) and TRB cDNA from the peripheral blood of one of the two speci-mens, and the human/dolphin amino acids multi-sequence alignments, allowed us to calculate the most likely interactions at the protein interface between the alpha/beta heterodimer in complex with major histocompatibility class I (MH1) protein. Interacting amino acids located in the com-plementarity-determining region according to IMGT numbering (CDR-IMGT) of the dolphin variable V-alpha and beta domains were identified. According to comparative modelization, the atom pair contact sites analysis between the human MH1 grove (G) domains and the T cell receptor (TR) V domains confirms conservation of the structure of the dolphin TR/pMH

Covid-19 patient management in outpatient setting: A population-based study from southern italy

Evidence on treatments for early-stage COVID-19 in outpatient setting is sparse. We explored the pattern of use of drugs prescribed for COVID-19 outpatients’ management in Southern Italy in the period February 2020–January 2021. This population-based cohort study was conducted using COVID-19 surveillance registry from Caserta Local Health Unit, which was linked to claims databases from the same catchment area. The date of SARS-CoV-2 infection diagnosis was the index date (ID). We evaluated demographic and clinical characteristics of the study drug users and the pattern of use of drugs prescribed for outpatient COVID-19 management. Overall, 40,030 patients were included in the analyses, with a median (IQR) age of 44 (27–58) years. More than half of the included patients were asymptomatic at the ID. Overall, during the study period, 720 (1.8%) patients died due to COVID-19. Azithromycin and glucocorticoids were the most frequently prescribed drugs, while oxygen was the less frequently prescribed therapy. The cumulative rate of recovery from COVID-19 was 84.2% at 30 days from ID and it was lower among older patients. In this study we documented that the drug prescribing patterns for COVID-19 treatment in an outpatient setting from Southern Italy was not supported from current evidence on beneficial therapies for early treatment of COVID-19, thus highlighting the need to implement strategies for improving appropriate drug prescribing in general practice

L'insegnamento di Francesco Barone. Una breve riflessione

Si evidenzia l'interesse filosofico del contributo di Barone alla moderna immagine fallibilista della scienz