IMGT®Homo sapiens IG and TR Loci, Gene Order, CNV and Haplotypes: New Concepts as a Paradigm for Jawed Vertebrates Genome Assemblies

Abstract

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.

Tetraploid Ancestry Provided Atlantic Salmon With Two Paralogue Functional T Cell Receptor Beta Regions Whereof One Is Completely Novel

“…Atlantic salmon TRB data generated here will be implemented in the IMGT database and thus be available to the scientific community. Nomenclature suggested here will be submitted for approval by the International Union of Immunological Societies (IUIS) Nomenclature Committee (NOM) Immunoglobulins (IG), T cell receptors (TR) and major histocompatibility (MH) SubCommittee (https://iuis.org/ committees/nom/immunoglobulins-ig-T cell-receptors-tr-andmajor-histocompatibility-mh-nomenclature-sub-committee/) (44) prior to being accepted as the official nomenclature.…”

IMGT® Nomenclature of Engineered IGHG Variants Involved in Antibody Effector Properties and Formats

“…The bridging of genes, structures and functions is based on the IMGT-ONTOLOGY axioms and concepts from which were generared the IMGT Scientific chart rules [ 78 , 79 , 80 , 81 , 82 ] ( Table 2 ): CLASSIFICATION for theIMGT standardized gene and allele nomenclature [ 1 , 2 , 3 , 4 , 5 , 7 , 8 , 9 , 10 , 61 , 62 , 63 ], IDENTIFICATION for IMGT standardized keywords and keyword abbreviations (e.g., clonotype, paratope and epitope, variant, Fc receptor and FcR) [ 53 , 54 ], DESCRIPTION forIMGT standardized labels [ 55 , 56 , 57 , 58 ] (e.g., complementarity determining region (CDR)-IMGT (CDR1-IMGT to CDR3-IMGT) [ 57 ] and framework region (FR-IMGT) (FR1-IMGT to FR4-IMGT) [ 58 ]), NUMEROTATION for the IMGT unique numbering [ 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 ] and the IMGT Colliers de Perles [ 51 , 73 , 74 , 75 , 76 , 77 ]. IMGT positions per domain are used in Protein displays, Alignments of alleles, CDR-IMGT lengths, Allotypes [ 59 , 60 ] sections of the IMGT Repertoire, and to number amino acids involved in paratope/epitope (antigen receptor V-domains/target interactions [ 83 ]) ...…”

“…The variants involved in complement-dependent cytotoxicity (CDC) reduction include six variants, of which three Homo sapiens IGHG1 variants: G1v8 ‘DLE’ [ 4 ], G1v19 [ 2 ] and G1v20 [ 2 , 39 ]; and three Mus musculus IGHG2B variants: Musmus G2Bv2 [ 7 ], Musmus G2Bv3 [ 7 ] and Musmus G2Bv4 [ 7 ] ( Table 9 ).…”

“…The variants involved in antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) reduction include 32 variants and four variant associations, of which 22 Homo sapiens IGHG1 variants: G1v4 [ 2 ], G1v14 ‘LALA’ [ 21 , 39 ], G1v14-1, G1v14-4, G1v14-48, G1v14-49 ‘LALAPG’ [ 40 ], G1v14-67, G1v23 [ 20 ], G1v38 [ 35 ], G1v39 ‘FES’ ‘TM’ [ 20 , 24 ], G1v40, G1v41 [ 20 , 24 ], G1v43, G1v48, G1v49 [ 40 ], G1v51, G1v53 ‘FQQ’, G1v59 [ 41 ], G1v60, G1v63, G1v65, G1v70 and one association G1v53-G1v21 ‘FQQ-YTE’ [ 38 ]; three Homo sapiens IGHG2 variants: G2v2 ‘IgG2m4′ [ 23 ], G2v3 ‘G2sigma’ [ 24 ] and the chimeric G2G4v1 [ 22 ]; five Homo sapiens IGHG4 variants: G4v3 ‘LE’ [ 20 ], G4v3-49 ‘LEPG’ [ 40 ], G4v4 ‘FALA’ [ 21 ], G4v7, G4v49 [ 40 ] and three associations G4v3-G4v5 ‘SPLE’ [ 12 , 20 ], G4v3-49-G4v5 ‘SPLEPG’ [ 40 ] [ 12 ] and G4v4-G4v5 ‘IgG4ProAlaAla’ [ 12 , 24 ] and two Canis lupus familiaris IGHG2 variants: CanlupfamG2v1 and CanlupfamG2v2 ( Table 10 ).…”

“…The adaptive immune response, acquired by jawed vertebrates (or gnathostomata ) more than 450 million years ago and found in all extant jawed vertebrate species from fish to humans, is characterized by a remarkable immune specificity and memory, which are the properties of the B and T cells because of the extreme diversity of their antigen receptors [ 1 ]. The antigen receptors of the adaptive immune response [ 1 , 2 ] comprise the immunoglobulins (IG) or antibodies of the B cells and plasmocytes [ 3 , 4 ] and the T cell receptors (TR) of the T cells [ 5 ]. The IG recognizes antigens in their native (unprocessed) form, whereas the TR recognizes processed antigens, which are presented as peptides through its highly polymorphic major histocompatibility (MH, in humans HLA for human leucocyte antigens) proteins [ 6 ].…”