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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

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          Abstract

          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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          IMGT unique numbering for immunoglobulin and T cell receptor variable domains and Ig superfamily V-like domains.

          IMGT, the international ImMunoGeneTics database (http://imgt.cines.fr) is a high quality integrated information system specializing in immunoglobulins (IG), T cell receptors (TR) and major histocompatibility complex (MHC) of human and other vertebrates. IMGT provides a common access to expertly annotated data on the genome, proteome, genetics and structure of the IG and TR, based on the IMGT Scientific chart and IMGT-ONTOLOGY. The IMGT unique numbering defined for the IG and TR variable regions and domains of all jawed vertebrates has allowed a redefinition of the limits of the framework (FR-IMGT) and complementarity determining regions (CDR-IMGT), leading, for the first time, to a standardized description of mutations, allelic polymorphisms, 2D representations (Colliers de Perles) and 3D structures, whatever the antigen receptor, the chain type, or the species. The IMGT numbering has been extended to the V-like domain and is, therefore, highly valuable for comparative analysis and evolution studies of proteins belonging to the IG superfamily.
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            Immunoglobulin and T Cell Receptor Genes: IMGT® and the Birth and Rise of Immunoinformatics

            IMGT®, the international ImMunoGeneTics information system® 1, (CNRS and Université Montpellier 2) is the global reference in immunogenetics and immunoinformatics. By its creation in 1989, IMGT® marked the advent of immunoinformatics, which emerged at the interface between immunogenetics and bioinformatics. IMGT® is specialized in the immunoglobulins (IG) or antibodies, T cell receptors (TR), major histocompatibility (MH), and proteins of the IgSF and MhSF superfamilies. IMGT® has been built on the IMGT-ONTOLOGY axioms and concepts, which bridged the gap between genes, sequences, and three-dimensional (3D) structures. The concepts include the IMGT® standardized keywords (concepts of identification), IMGT® standardized labels (concepts of description), IMGT® standardized nomenclature (concepts of classification), IMGT unique numbering, and IMGT Colliers de Perles (concepts of numerotation). IMGT® comprises seven databases, 15,000 pages of web resources, and 17 tools, and provides a high-quality and integrated system for the analysis of the genomic and expressed IG and TR repertoire of the adaptive immune responses. Tools and databases are used in basic, veterinary, and medical research, in clinical applications (mutation analysis in leukemia and lymphoma) and in antibody engineering and humanization. They include, for example IMGT/V-QUEST and IMGT/JunctionAnalysis for nucleotide sequence analysis and their high-throughput version IMGT/HighV-QUEST for next-generation sequencing (500,000 sequences per batch), IMGT/DomainGapAlign for amino acid sequence analysis of IG and TR variable and constant domains and of MH groove domains, IMGT/3Dstructure-DB for 3D structures, contact analysis and paratope/epitope interactions of IG/antigen and TR/peptide-MH complexes and IMGT/mAb-DB interface for therapeutic antibodies and fusion proteins for immune applications (FPIA).
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              IMGT unique numbering for immunoglobulin and T cell receptor constant domains and Ig superfamily C-like domains.

              IMGT, the international ImMunoGeneTics information system (http://imgt.cines.fr) provides a common access to expertly annotated data on the genome, proteome, genetics and structure of immunoglobulins (IG), T cell receptors (TR), major histocompatibility complex (MHC), and related proteins of the immune system (RPI) of human and other vertebrates. The NUMEROTATION concept of IMGT-ONTOLOGY has allowed to define a unique numbering for the variable domains (V-DOMAINs) and for the V-LIKE-DOMAINs. In this paper, this standardized characterization is extended to the constant domains (C-DOMAINs), and to the C-LIKE-DOMAINs, leading, for the first time, to their standardized description of mutations, allelic polymorphisms, two-dimensional (2D) representations and tridimensional (3D) structures. The IMGT unique numbering is, therefore, highly valuable for the comparative, structural or evolutionary studies of the immunoglobulin superfamily (IgSF) domains, V-DOMAINs and C-DOMAINs of IG and TR in vertebrates, and V-LIKE-DOMAINs and C-LIKE-DOMAINs of proteins other than IG and TR, in any species.
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                Author and article information

                Journal
                Genes (Basel)
                Genes (Basel)
                genes
                Genes
                MDPI
                2073-4425
                05 June 2020
                June 2020
                : 11
                : 6
                : 624
                Affiliations
                [1 ]Department of Biology, University of Bari “Aldo Moro”, 70124 Bari, Italy; giovanna.linguiti@ 123456uniba.it (G.L.); salvatricemaria.ciccarese@ 123456uniba.it (S.C.)
                [2 ]Department of Biological and Environmental Science and Technologies, University of Salento, 73100 Lecce, Italy; sara.massari@ 123456unisalento.it
                [3 ]Department of Agricultural and Environmental Science, University of Bari “Aldo Moro”, 70124 Bari, Italy; anna.caputijambrenghi@ 123456uniba.it (A.C.J.); francesco.giannico@ 123456uniba.it (F.G.)
                [4 ]IMGT ®, the International ImMunoGeneTics Information System ®, Laboratoire d’ImmunoGénétique Moléculaire LIGM, Institut de Génétique Humaine IGH, UMR9002 CNRS, Université de Montpellier, CEDEX 5, 34396 Montpellier, France; marie-paule.lefranc@ 123456igh.cnrs.fr
                Author notes
                Author information
                https://orcid.org/0000-0002-5601-1118
                https://orcid.org/0000-0002-0773-0044
                https://orcid.org/0000-0003-4025-4956
                https://orcid.org/0000-0003-3208-0730
                Article
                genes-11-00624
                10.3390/genes11060624
                7349638
                32517024
                1dfb7cd9-5663-4601-a696-ef5835763a81
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 28 April 2020
                : 02 June 2020
                Categories
                Review

                t cell receptor,trg locus,trg genes,immunogenomics,evolution,mammals,imgt

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