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1.
Methods Mol Biol ; 2552: 3-59, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36346584

RESUMO

IMGT®, the international ImMunoGeneTics information system®, http://www.imgt.org , the global reference in immunogenetics and immunoinformatics, was created in 1989 by Marie-Paule Lefranc (Université de Montpellier and CNRS) to manage the huge diversity of the antigen receptors, immunoglobulins (IG) or antibodies, and T cell receptors (TR) of the adaptive immune responses. The founding of IMGT® marked the advent of immunoinformatics, which emerged at the interface between immunogenetics and bioinformatics. IMGT® standardized analysis of the IG, TR, and major histocompatibility (MH) genes and proteins bridges the gap between sequences and three-dimensional (3D) structures, for all jawed vertebrates from fish to humans. This is achieved through the IMGT Scientific chart rules, based on the IMGT-ONTOLOGY axioms, and primarily CLASSIFICATION (IMGT gene and allele nomenclature) and NUMEROTATION (IMGT unique numbering and IMGT Colliers de Perles). IMGT® comprises seven databases (IMGT/LIGM-DB for nucleotide sequences, IMGT/GENE-DB for genes and alleles, etc.), 17 tools (IMGT/V-QUEST, IMGT/JunctionAnalysis, IMGT/HighV-QUEST for NGS, etc.), and more than 20,000 Web resources. In this chapter, the focus is on the tools for amino acid sequences per domain (IMGT/DomainGapAlign and IMGT/Collier-de-Perles), and on the databases for receptors (IMGT/2Dstructure-DB and IMGT/3D-structure-DB) described per receptor, chain, and domain and, for 3D, with contact analysis, paratope, and epitope. The IMGT/mAb-DB is the query interface for monoclonal antibodies (mAb), fusion proteins for immune applications (FPIA), composite proteins for clinical applications (CPCA), and related proteins of interest (RPI) with links to IMGT® 2D and 3D databases and to the World Health Organization (WHO) International Nonproprietary Names (INN) program lists. The chapter includes the human IG allotypes and antibody engineered variants for effector properties used in the description of therapeutical mAb.


Assuntos
Imunogenética , Imunoglobulinas , Humanos , Animais , Imunogenética/métodos , Imunoglobulinas/genética , Imunoglobulinas/química , Anticorpos/genética , Biologia Computacional/métodos , Sequência de Aminoácidos , Receptores de Antígenos de Linfócitos T/genética
2.
Antibodies (Basel) ; 11(4)2022 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-36278618

RESUMO

The constant region of the immunoglobulin (IG) or antibody heavy gamma chain is frequently engineered to modify the effector properties of the therapeutic monoclonal antibodies. These variants are classified in regards to their effects on effector functions, antibody-dependent cytotoxicity (ADCC), antibody-dependent phagocytosis (ADCP), complement-dependent cytotoxicity (CDC) enhancement or reduction, B cell inhibition by the coengagement of antigen and FcγR on the same cell, on half-life increase, and/or on structure such as prevention of IgG4 half-IG exchange, hexamerisation, knobs-into-holes and the heteropairing H-H of bispecific antibodies, absence of disulfide bridge inter H-L, absence of glycosylation site, and site-specific drug attachment engineered cysteine. The IMGT engineered variant identifier is comprised of the species and gene name (and eventually allele), the letter 'v' followed by a number (assigned chronologically), and for each concerned domain (e.g, CH1, h, CH2 and CH3), the novel AA (single letter abbreviation) and IMGT position according to the IMGT unique numbering for the C-domain and between parentheses, the Eu numbering. IMGT engineered variants are described with detailed amino acid changes, visualized in motifs based on the IMGT numbering bridging genes, sequences, and structures for higher order description.

3.
Front Immunol ; 13: 928860, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36016959

RESUMO

The Camelidae species occupy an important immunological niche within the humoral as well as cell mediated immune response. Although recent studies have highlighted that the somatic hypermutation (SHM) shapes the T cell receptor gamma (TRG) and delta (TRD) repertoire in Camelus dromedarius, it is still unclear how γδ T cells use the TRG/TRD receptors and their respective variable V-GAMMA and V-DELTA domains to recognize antigen in an antibody-like fashion. Here we report about 3D structural analyses of the human and dromedary γδ T cell receptor. First, we have estimated the interaction energies at the interface within the human crystallized paired TRG/TRD chains and quantified interaction energies within the same human TRG/TRD chains in complex with the CD1D, an RPI-MH1-LIKE antigen presenting glycoprotein. Then, we used the human TRG/TRD-CD1D complex as template for the 3D structure of the dromedary TRG/TRD-CD1D complex and for guiding the 3D human/dromedary comparative analysis. The choice of mutated TRG alternatively combined with mutated TRD cDNA clones originating from the spleen of one single dromedary was crucial to quantify the strength of the interactions at the protein-protein interface between the paired C. dromedarius TRG and TRD V-domains and between the C. dromedarius TRG/TRD V-domains and CD1D G-domains. Interacting amino acids located in the V-domain Complementarity Determining Regions (CDR) and Framework Regions (FR) according to the IMGT unique numbering for V-domains were identified. The resulting 3D dromedary TRG V-GAMMA combined with TRD V-DELTA protein complexes allowed to deduce the most stable gamma/delta chains pairings and to propose a candidate CD1D-restricted γδ T cell receptor complex.


Assuntos
Camelus , Receptores de Antígenos de Linfócitos T gama-delta , Animais , Antígenos CD1d/genética , Células Clonais , Regiões Determinantes de Complementaridade/genética , DNA Complementar , Humanos , Receptores de Antígenos de Linfócitos T gama-delta/química , Receptores de Antígenos de Linfócitos T gama-delta/genética
4.
MAbs ; 14(1): 2075078, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35584276

RESUMO

Appropriate nomenclature for all pharmaceutical substances is important for clinical development, licensing, prescribing, pharmacovigilance, and identification of counterfeits. Nonproprietary names that are unique and globally recognized for all pharmaceutical substances are assigned by the International Nonproprietary Names (INN) Programme of the World Health Organization (WHO). In 1991, the INN Programme implemented the first nomenclature scheme for monoclonal antibodies. To accompany biotechnological development, this nomenclature scheme has evolved over the years; however, since the scheme was introduced, all pharmacological substances that contained an immunoglobulin variable domain were coined with the stem -mab. To date, there are 879 INN with the stem -mab. Owing to this high number of names ending in -mab, devising new and distinguishable INN has become a challenge. The WHO INN Expert Group therefore decided to revise the system to ease this situation. The revised system was approved and adopted by the WHO at the 73rd INN Consultation held in October 2021, and the radical decision was made to discontinue the use of the well-known stem -mab in naming new antibody-based drugs and going forward, to replace it with four new stems: -tug, -bart, -mig, and -ment.


Assuntos
Anticorpos Monoclonais , Preparações Farmacêuticas , Organização Mundial da Saúde
5.
Methods Mol Biol ; 2453: 477-531, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35622340

RESUMO

The variable domains (V-DOMAIN) of the antigen receptors, immunoglobulins (IG) or antibodies and T cell receptors (TR), which specifically recognize the antigens show a huge diversity in their sequences. This diversity results from the complex mechanisms involved in the synthesis of these domains at the DNA level (rearrangements of the variable (V), diversity (D), and joining (J) genes; N-diversity; and, for the IG, somatic hypermutations). The recognition of V, D, and J as "genes" and their entry in databases mark the creation of IMGT by Marie-Paule Lefranc, and the origin of immunoinformatics in 1989. For 30 years, IMGT®, the international ImMunoGeneTics information system® http://www.imgt.org , has implemented databases and developed tools for IG and TR immunoinformatics, based on the IMGT Scientific chart rules and IMGT-ONTOLOGY concepts and axioms, and more particularly, the princeps ones: IMGT genes and alleles (CLASSIFICATION axiom) and the IMGT unique numbering and IMGT Collier de Perles (NUMEROTATION axiom). This chapter describes the online tools for the characterization and annotation of the expressed V-DOMAIN sequences: (a) IMGT/V-QUEST analyzes in detail IG and TR rearranged nucleotide sequences, (b) IMGT/HighV-QUEST is its high throughput version, which includes a module for the identification of IMGT clonotypes and generates immunoprofiles of expressed V, D, and J genes and alleles, (c) IMGT/StatClonotype performs the pairwise comparison of IMGT/HighV-QUEST immunoprofiles, (d) IMGT/DomainGapAlign analyzes amino acid sequences and is frequently used in antibody engineering and humanization, and (e) IMGT/Collier-de-Perles provides two-dimensional (2D) graphical representations of V-DOMAIN, bridging the gap between sequences and 3D structures. These IMGT® tools are widely used in repertoire analyses of the adaptive immune responses in normal and pathological situations and in the design of engineered IG and TR for therapeutic applications.


Assuntos
Biologia Computacional , Imunogenética , Sequência de Aminoácidos , Anticorpos/genética , Biologia Computacional/métodos , Imunogenética/métodos , Receptores de Antígenos de Linfócitos T/química , Receptores de Antígenos de Linfócitos T/genética
6.
Methods Mol Biol ; 2453: 533-570, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35622341

RESUMO

T-cell receptors (TR), the antigen receptors of T cells, specifically recognize peptides presented by the major histocompatibility (MH) proteins, as peptide/MH (pMH), on the cell surface. The structure characterization of the trimolecular TR/pMH complexes is crucial to the fields of immunology, vaccination, and immunotherapy. IMGT/3Dstructure-DB is the three-dimensional (3-D) structure database of IMGT®, the international ImMunoGenetics information system®. By its creation, IMGT® marks the advent of immunoinformatics, which emerged at the interface between immunogenetics and bioinformatics. The IMGT® immunoglobulin (IG) and TR gene and allele nomenclature (CLASSIFICATION axiom) and the IMGT unique numbering and IMGT/Collier-de-Perles (NUMEROTATION axiom) are the two founding breakthroughs of immunoinformatics. IMGT-ONTOLOGY concepts and IMGT Scientific chart rules generated from these axioms allowed IMGT® bridging genes, structures, and functions. IMGT/3Dstructure-DB contains 3-D structures of IG or antibodies, TR and MH proteins of the adaptive immune responses of jawed vertebrates (gnathostomata), IG or TR complexes with antigens (IG/Ag, TR/pMH), related proteins of the immune system of any species belonging to the IG and MH superfamilies, and fusion proteins for immune applications. The focus of this chapter is on the TR V domains and MH G domains and the contact analysis comparison in TR/pMH interactions. Standardized molecular characterization includes "IMGT pMH contact sites" for peptide and MH groove interactions and "IMGT paratopes and epitopes" for TR/pMH complexes. Data are available in the IMGT/3Dstructure database, at the IMGT Home page http://www.imgt.org .


Assuntos
Anticorpos , Receptores de Antígenos de Linfócitos T , Animais , Sítios de Ligação de Anticorpos , Proteínas de Transporte , Epitopos , Histocompatibilidade , Peptídeos , Receptores de Antígenos de Linfócitos T/química , Receptores de Antígenos de Linfócitos T/genética
7.
Vaccines (Basel) ; 10(3)2022 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-35335026

RESUMO

The adaptive immune system, along with the innate immune system, are the two main biological processes that protect an organism from pathogens. The adaptive immune system is characterized by the specificity and extreme diversity of its antigen receptors. These antigen receptors are the immunoglobulins (IG) or antibodies of the B cells and the T cell receptors (TR) of the T cells. The IG are proteins that have a dual role in immunity: they recognize antigens and trigger elimination mechanisms, to rid the body of foreign cells. The synthesis of the immunoglobulin heavy and light chains requires gene rearrangements at the DNA level in the IGH, IGK, and IGL loci. The rhesus monkey (Macaca mulatta) is one of the most widely used nonhuman primate species in biomedical research. In this manuscript, we provide a thorough analysis of the three IG loci of the Mmul_10 assembly of rhesus monkey, integrating IMGT previously existing data. Detailed characterization of IG genes includes their localization and position in the loci, the determination of the allele functionality, and the description of the regulatory elements of their promoters as well as the sequences of the conventional recombination signals (RS). This complete annotation of the genomic IG loci of Mmul_10 assembly and the highly detailed IG gene characterization could be used as a model, in additional rhesus monkey assemblies, for the analysis of the IG allelic polymorphism and structural variation, which have been described in rhesus monkeys.

8.
Biomolecules ; 12(3)2022 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-35327572

RESUMO

IMGT®, the international ImMunoGeneTics information system®, created in 1989, by Marie-Paule Lefranc (Université de Montpellier and CNRS), marked the advent of immunoinformatics, a new science which emerged at the interface between immunogenetics and bioinformatics for the study of the adaptive immune responses. IMGT® is based on a standardized nomenclature of the immunoglobulin (IG) and T cell receptor (TR) genes and alleles from fish to humans and on the IMGT unique numbering for the variable (V) and constant (C) domains of the immunoglobulin superfamily (IgSF) of vertebrates and invertebrates, and for the groove (G) domain of the major histocompatibility (MH) and MH superfamily (MhSF) proteins. IMGT® comprises 7 databases, 17 tools and more than 25,000 pages of web resources for sequences, genes and structures, based on the IMGT Scientific chart rules generated from the IMGT-ONTOLOGY axioms and concepts. IMGT® reference directories are used for the analysis of the NGS high-throughput expressed IG and TR repertoires (natural, synthetic and/or bioengineered) and for bridging sequences, two-dimensional (2D) and three-dimensional (3D) structures. This manuscript focuses on the IMGT®Homo sapiens IG and TR loci, gene order, copy number variation (CNV) and haplotypes new concepts, as a paradigm for jawed vertebrates genome assemblies.


Assuntos
Variações do Número de Cópias de DNA , Imunoglobulinas , Animais , Ordem dos Genes , Haplótipos/genética , Humanos , Imunoglobulinas/genética , Vertebrados/genética
9.
Front Immunol ; 12: 753960, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34733285

RESUMO

In jawed vertebrates, two major T cell populations have been characterized. They are defined as α/ß or γ/δ T cells, based on the expressed T cell receptor. Salmonids (family Salmonidae) include two key teleost species for aquaculture, rainbow trout (Oncorhynchus mykiss) and Atlantic salmon (Salmo salar) which constitute important models for fish immunology and important targets for vaccine development. The growing interest to decipher the dynamics of adaptive immune responses against pathogens or vaccines has resulted in recent efforts to sequence the immunoglobulin (IG) or antibodies and T cell receptor (TR) repertoire in these species. In this context, establishing a comprehensive and coherent locus annotation is the fundamental basis for the analysis of high-throughput repertoire sequencing data. We therefore decided to revisit the description and annotation of TRA/TRD locus in Atlantic salmon and two strains of rainbow trout (Swanson and Arlee) using the now available high-quality genome assemblies. Phylogenetic analysis of functional TRA/TRD V genes from these three genomes led to the definition of 25 subgroups shared by both species, some with particular feature. A total of 128 TRAJ genes were identified in Salmo, the majority with a close counterpart in Oncorhynchus. Analysis of expressed TRA repertoire indicates that most TRAV gene subgroups are expressed at mucosal and systemic level. The present work on TRA/TRD locus annotation along with the analysis of TRA repertoire sequencing data show the feasibility and advantages of a common salmonid TRA/TRD nomenclature that allows an accurate annotation and analysis of high-throughput sequencing results, across salmonid T cell subsets.


Assuntos
Genes Codificadores dos Receptores de Linfócitos T/genética , Oncorhynchus mykiss/genética , Receptores de Antígenos de Linfócitos T/genética , Salmo salar/genética , Sequência de Aminoácidos , Animais , Sequência Conservada , Perfilação da Expressão Gênica , Biblioteca Gênica , Genoma , Modelos Moleculares , Anotação de Sequência Molecular , Oncorhynchus mykiss/imunologia , Filogenia , Conformação Proteica , RNA Mensageiro/genética , Receptores de Antígenos de Linfócitos T/biossíntese , Receptores de Antígenos de Linfócitos T/química , Salmo salar/imunologia , Alinhamento de Sequência , Homologia de Sequência de Aminoácidos , Especificidade da Espécie , Terminologia como Assunto
10.
Elife ; 102021 05 26.
Artigo em Inglês | MEDLINE | ID: mdl-34037521

RESUMO

Use of adaptive immune receptor repertoire sequencing (AIRR-seq) has become widespread, providing new insights into the immune system with potential broad clinical and diagnostic applications. However, like many high-throughput technologies, it comes with several problems, and the AIRR Community was established to understand and help solve them. We, the AIRR Community's Biological Resources Working Group, have surveyed scientists about the need for standards and controls in generating and annotating AIRR-seq data. Here, we review the current status of AIRR-seq, provide the results of our survey, and based on them, offer recommendations for developing AIRR-seq standards and controls, including future work.


Assuntos
Imunidade Adaptativa/genética , Perfilação da Expressão Gênica/normas , RNA-Seq/normas , Receptores Imunológicos/genética , Transcriptoma , Animais , Bases de Dados Genéticas , Humanos , Variações Dependentes do Observador , Controle de Qualidade , Padrões de Referência , Reprodutibilidade dos Testes
11.
Genes (Basel) ; 12(4)2021 04 14.
Artigo em Inglês | MEDLINE | ID: mdl-33919966

RESUMO

The bottlenose dolphin (Tursiops truncatus) belongs to the Cetartiodactyla and, similarly to other cetaceans, represents the most successful mammalian colonization of the aquatic environment. 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 uniqueness 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 rearranged T cell receptor α (TRA) and TRB cDNA from the peripheral blood of one of the two specimens, 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 complementarity-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.


Assuntos
Golfinho Nariz-de-Garrafa/genética , Receptores de Antígenos de Linfócitos T alfa-beta/genética , Análise de Sequência de DNA/métodos , Análise de Sequência de Proteína/métodos , Animais , Mapeamento Cromossômico , Feminino , Rearranjo Gênico da Cadeia alfa dos Receptores de Antígenos dos Linfócitos T , Rearranjo Gênico da Cadeia beta dos Receptores de Antígenos dos Linfócitos T , Antígenos de Histocompatibilidade Classe I/metabolismo , Humanos , Masculino , Receptores de Antígenos de Linfócitos T alfa-beta/metabolismo , Alinhamento de Sequência , Microglobulina beta-2/metabolismo
12.
Dev Comp Immunol ; 118: 103998, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33450314

RESUMO

High-throughput sequencing technologies brought a renewed interest for immune repertoires. Fish Ab and B cell repertoires are no exception, and their comprehensive analysis can both provide new insights into poorly understood immune mechanisms, and identify markers of protection after vaccination. However, the lack of genomic description and standardized nomenclature of IG genes hampers accurate annotation of Ig mRNA deep sequencing data. Complete genome sequences of Atlantic salmon and rainbow trout (Swanson line) recently allowed us to establish a comprehensive and coherent annotation of Salmonid IGH genes following IMGT standards. Here we analyzed the IGHV, D, and J genes from the newly released genome of a second rainbow trout line (Arlee). We confirmed the validity of salmonid IGHV subgroups, and extended the description of the rainbow trout IGH gene repertoire with novel sequences, while keeping nomenclature continuity. This work provides an important resource for annotation of high-throughput Ab repertoire sequencing data.


Assuntos
Genes de Cadeia Pesada de Imunoglobulina/genética , Oncorhynchus mykiss/genética , Recombinação V(D)J/imunologia , Animais , Sequenciamento de Nucleotídeos em Larga Escala , Anotação de Sequência Molecular , Oncorhynchus mykiss/imunologia , Filogenia
13.
Genes (Basel) ; 12(1)2020 12 28.
Artigo em Inglês | MEDLINE | ID: mdl-33379283

RESUMO

The adaptive immune response provides the vertebrate immune system with the ability to recognize and remember specific pathogens to generate immunity, and mount stronger attacks each time the pathogen is encountered. T cell receptors are the antigen receptors of the adaptive immune response expressed by T cells, which specifically recognize processed antigens, presented as peptides by the highly polymorphic major histocompatibility (MH) proteins. T cell receptors (TR) are divided into two groups, αß and γδ, which express distinct TR containing either α and ß, or γ and δ chains, respectively. The TRα locus (TRA) and TRδ locus (TRD) of bovine (Bos taurus) and the sheep (Ovis aries) have recently been described and annotated by IMGT® biocurators. The aim of the present study is to present the results of the biocuration and to compare the genes of the TRA/TRD loci among these ruminant species based on the Homo sapiens repertoire. The comparative analysis shows similarities but also differences, including the fact that these two species have a TRA/TRD locus about three times larger than that of humans and therefore have many more genes which may demonstrate duplications and/or deletions during evolution.


Assuntos
Bovinos/genética , Genes Codificadores da Cadeia alfa de Receptores de Linfócitos T/genética , Genes Codificadores da Cadeia delta de Receptores de Linfócitos T/genética , Loci Gênicos/imunologia , Carneiro Doméstico/genética , Imunidade Adaptativa/genética , Animais , Bovinos/imunologia , Evolução Molecular , Anotação de Sequência Molecular , Carneiro Doméstico/imunologia , Especificidade da Espécie
14.
JCI Insight ; 5(22)2020 11 19.
Artigo em Inglês | MEDLINE | ID: mdl-33048842

RESUMO

Plasma antimalarial Ab can mediate antiparasite immunity but has not previously been characterized at the molecular level. Here, we develop an innovative strategy to characterize humoral responses by integrating profiles of plasma immunoglobulins (IGs) or Abs with those expressed on B cells as part of the B cell receptor. We applied this strategy to define plasma IG and to determine variable (V) gene usage after vaccination with the Plasmodium falciparum zygote antigen Pfs25. Using proteomic tools coupled with bulk immunosequencing data, we determined human antigen-binding fragment [F(ab')2] peptide sequences from plasma IG of adults who received 4 doses of Pfs25-EPA/Alhydrogel. Specifically, Pfs25 antigen-specific F(ab')2 peptides (Pfs25-IG) were aligned to cDNA sequences of IG heavy (IGH) chain complementarity determining region 3 from a data set generated by total peripheral B cell immunosequencing of the entire vaccinated population. IGHV4 was the most commonly identified IGHV subgroup of Pfs25-IG, a pattern that was corroborated by V heavy/V light chain sequencing of Pfs25-specific single B cells from 5 vaccinees and by matching plasma Pfs25-IG peptides and V-(D)-J sequences of Pfs25-specific single B cells from the same donor. Among 13 recombinant human mAbs generated from IG sequences of Pfs25-specific single B cells, a single IGHV4 mAb displayed strong neutralizing activity, reducing the number of P. falciparum oocysts in infected mosquitoes by more than 80% at 100 µg/mL. Our approach characterizes the human plasma Ab repertoire in response to the Pfs25-EPA/Alhydrogel vaccine and will be useful for studying circulating Abs in response to other vaccines as well as those induced during infections or autoimmune disorders.


Assuntos
Anticorpos Antiprotozoários/sangue , Antimaláricos/imunologia , Linfócitos B/imunologia , Imunoglobulinas/sangue , Malária Falciparum/sangue , Plasmodium falciparum/imunologia , Proteínas de Protozoários/imunologia , Adjuvantes Imunológicos , Adolescente , Adulto , Anticorpos Monoclonais/sangue , Anticorpos Monoclonais/imunologia , Anticorpos Antiprotozoários/imunologia , Antígenos de Protozoários/imunologia , Antimaláricos/administração & dosagem , Ensaios Clínicos como Assunto , Feminino , Humanos , Imunoglobulinas/imunologia , Vacinas Antimaláricas/administração & dosagem , Vacinas Antimaláricas/imunologia , Malária Falciparum/imunologia , Malária Falciparum/parasitologia , Malária Falciparum/prevenção & controle , Masculino , Pessoa de Meia-Idade , Vacinação , Adulto Jovem
15.
Biomedicines ; 8(9)2020 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-32878258

RESUMO

IMGT®, the international ImMunoGeneTics® information system founded in 1989 by Marie-Paule Lefranc (Université de Montpellier and CNRS), marked the advent of immunoinformatics, a new science at the interface between immunogenetics and bioinformatics. For the first time, the immunoglobulin (IG) or antibody and T cell receptor (TR) genes were officially recognized as 'genes' as well as were conventional genes. This major breakthrough has allowed the entry, in genomic databases, of the IG and TR variable (V), diversity (D) and joining (J) genes and alleles of Homo sapiens and of other jawed vertebrate species, based on the CLASSIFICATION axiom. The second major breakthrough has been the IMGT unique numbering and the IMGT Collier de Perles for the V and constant (C) domains of the IG and TR and other proteins of the IG superfamily (IgSF), based on the NUMEROTATION axiom. IMGT-ONTOLOGY axioms and concepts bridge genes, sequences, structures and functions, between biological and computational spheres in the IMGT® system (Web resources, databases and tools). They provide the IMGT Scientific chart rules to identify, to describe and to analyse the IG complex molecular data, the huge diversity of repertoires, the genetic (alleles, allotypes, CNV) polymorphisms, the IG dual function (paratope/epitope, effector properties), the antibody humanization and engineering.

16.
Genes (Basel) ; 11(6)2020 06 05.
Artigo em Inglês | MEDLINE | ID: mdl-32517024

RESUMO

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 αß or γδ chains. The diversity of the TRs is mainly due to the unique organization of the genes encoding the α, ß, 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.


Assuntos
Imunidade Adaptativa/genética , Evolução Molecular , Genoma/genética , Receptores de Antígenos de Linfócitos T/genética , Imunidade Adaptativa/imunologia , Sequência de Aminoácidos/genética , Animais , Genoma/imunologia , Genômica , Humanos , Mamíferos/genética , Mamíferos/imunologia , Filogenia , Receptores de Antígenos de Linfócitos T/imunologia
17.
BMC Genomics ; 21(1): 20, 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31906850

RESUMO

BACKGROUND: The domestic cat (Felis catus) is an important companion animal and is used as a large animal model for human disease. However, the comprehensive study of adaptive immunity in this species is hampered by the lack of data on lymphocyte antigen receptor genes and usage. The objectives of this study were to annotate the feline T cell receptor (TR) loci and to characterize the expressed repertoire in lymphoid organs of normal cats using high-throughput sequencing. RESULTS: The Felis catus TRG locus contains 30 genes: 12 TRGV, 12 TRGJ and 6 TRGC, the TRB locus contains 48 genes: 33 TRBV, 2 TRBD, 11 TRBJ, 2 TRBC, the TRD locus contains 19 genes: 11 TRDV, 2 TRDD, 5 TRDJ, 1 TRDC, and the TRA locus contains 127 genes: 62 TRAV, 64 TRAJ, 1 TRAC. Functional feline V genes form monophyletic clades with their orthologs, and clustering of multimember subgroups frequently occurs in V genes located at the 5' end of TR loci. Recombination signal (RS) sequences of the heptamer and nonamer of functional V and J genes are highly conserved. Analysis of the TRG expressed repertoire showed preferential intra-cassette over inter-cassette rearrangements and dominant usage of the TRGV2-1 and TRGJ1-2 genes. The usage of TRBV genes showed minor bias but TRBJ genes of the second J-C-cluster were more commonly rearranged than TRBJ genes of the first cluster. The TRA/TRD V genes almost exclusively rearranged to J genes within their locus. The TRAV/TRAJ gene usage was relatively balanced while the TRD repertoire was dominated by TRDJ3. CONCLUSIONS: This is the first description of all TR loci in the cat. The genomic organization of feline TR loci was similar to that of previously described jawed vertebrates (gnathostomata) and is compatible with the birth-and-death model of evolution. The large-scale characterization of feline TR genes provides comprehensive baseline data on immune repertoires in healthy cats and will facilitate the development of improved reagents for the diagnosis of lymphoproliferative diseases in cats. In addition, these data might benefit studies using cats as a large animal model for human disease.


Assuntos
Gatos/genética , Loci Gênicos/genética , Tecido Linfoide/metabolismo , Receptores de Antígenos de Linfócitos T/genética , Imunidade Adaptativa/genética , Sequência de Aminoácidos , Animais , Gatos/imunologia , Genômica/métodos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Filogenia , Receptores de Antígenos de Linfócitos T/classificação , Homologia de Sequência de Aminoácidos
18.
Front Immunol ; 10: 2541, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31798572

RESUMO

In teleost fish as in mammals, humoral adaptive immunity is based on B lymphocytes expressing highly diverse immunoglobulins (IG). During B cell differentiation, IG loci are subjected to genomic rearrangements of V, D, and J genes, producing a unique antigen receptor expressed on the surface of each lymphocyte. During the course of an immune response to infections or immunizations, B cell clones specific of epitopes from the immunogen are expanded and activated, leading to production of specific antibodies. Among teleost fish, salmonids comprise key species for aquaculture. Rainbow trout (Oncorhynchus mykiss) and Atlantic salmon (Salmo salar) are especially important from a commercial point of view and have emerged as critical models for fish immunology. The growing interest to capture accurate and comprehensive antibody responses against common pathogens and vaccines has resulted in recent efforts to sequence the IG repertoire in these species. In this context, a unified and standardized nomenclature of salmonid IG heavy chain (IGH) genes is urgently required, to improve accuracy of annotation of adaptive immune receptor repertoire dataset generated by high-throughput sequencing (AIRRseq) and facilitate comparisons between studies and species. Interestingly, the assembly of salmonids IGH genomic sequences is challenging due to the presence of two large size duplicated IGH loci and high numbers of IG genes and pseudogenes. We used data available for Atlantic salmon to establish an IMGT standardized nomenclature of IGH genes in this species and then applied the IMGT rules to the rainbow trout IGH loci to set up a nomenclature, which takes into account the specificities of Salmonid loci. This unique, consistent nomenclature for Salmonid IGH genes was then used to construct IMGT sequence reference directories allowing accurate annotation of AIRRseq data. The complex issues raised by the genetic diversity of salmon and trout strains are discussed in the context of IG repertoire annotation.


Assuntos
Genes de Cadeia Pesada de Imunoglobulina , Anotação de Sequência Molecular , Oncorhynchus mykiss/genética , Salmo salar/genética , Animais , Biologia Computacional , Regulação da Expressão Gênica , Variação Genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Anotação de Sequência Molecular/métodos , Filogenia , Recombinação V(D)J
19.
Antibodies (Basel) ; 8(2)2019 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-31544835

RESUMO

At the 10th Human Genome Mapping (HGM10) Workshop, in New Haven, for the first time, immunoglobulin (IG) or antibody and T cell receptor (TR) variable (V), diversity (D), joining (J), and constant (C) genes were officially recognized as 'genes', as were the conventional genes. Under these HGM auspices, IMGT®, the international ImMunoGeneTics information system®, was created in June 1989 at Montpellier (University of Montpellier and CNRS). The creation of IMGT® marked the birth of immunoinformatics, a new science, at the interface between immunogenetics and bioinformatics. The accuracy and the consistency between genes and alleles, sequences, and three-dimensional (3D) structures are based on the IMGT Scientific chart rules generated from the IMGT-ONTOLOGY axioms and concepts: IMGT standardized keywords (IDENTIFICATION), IMGT gene and allele nomenclature (CLASSIFICATION), IMGT standardized labels (DESCRIPTION), IMGT unique numbering and IMGT Collier de Perles (NUMEROTATION). These concepts provide IMGT® immunoinformatics insights for antibody V and C domain structure and function, used for the standardized description in IMGT® web resources, databases and tools, immune repertoires analysis, single cell and/or high-throughput sequencing (HTS, NGS), antibody humanization, and antibody engineering in relation with effector properties.

20.
Eur J Immunol ; 49(12): 2146-2158, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31355919

RESUMO

The rabbit has been widely used in immunology and infectiology. Rabbit immunoglobulins have been extensively studied, leading to the discovery of their idiotypes, allotypic diversity, and of the diversification of the primary repertoire by hyperconversion. Much less is known about rabbit T cell receptors (TR), especially TRA. This isotype is particularly important for innate-like T cells, which typically express invariant TRA (iTRA). The presence of such cells in the rabbit remains an enigma. Rabbit NKT cells seem to be very rare, and lagomorphs lack MAIT cells. TRAV1, the variable gene expressed in the iTRA of these cells across most mammals, and MR1, the MH1-like receptor that present riboflavin derivatives to MAIT cells, are missing in rabbit. An alternative iTRA has been identified, that may be expressed by new innate-like T cells. To facilitate TRA repertoire analyses in rabbit, we report here a full description of TRA and TRD loci and a subgroup definition based on IMGT® classification. Rabbit TRA rearrangements follow the same temporal pattern that is observed in mouse and human. Rare transcripts expressing TRDV/TRDD/TRDJ rearrangements spliced to TRAC were detected. TRA and TRD genes have been made available in IMGT and IMGT/HighV-QUEST, allowing easy analysis of TRA/TRD RepSeq.


Assuntos
Loci Gênicos , Imunidade Inata/genética , Células T Matadoras Naturais , Receptores de Antígenos de Linfócitos T/genética , Animais , Humanos , Camundongos , Coelhos , Receptores de Antígenos de Linfócitos T/imunologia
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