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Front Immunol. 2019 Mar 18;10:435. doi: 10.3389/fimmu.2019.00435. eCollection 2019.

Inferred Allelic Variants of Immunoglobulin Receptor Genes: A System for Their Evaluation, Documentation, and Naming.

Author information

1
Department of Immunotechnology, Lund University, Lund, Sweden.
2
Center for HIV and STIs, National Institute for Communicable Diseases, Johannesburg, South Africa.
3
Faculty of Health Sciences, School of Pathology, University of the Witwatersrand, Johannesburg, South Africa.
4
Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, Stockholm, Sweden.
5
Institute of Structural and Molecular Biology, Birkbeck College, University of London, London, United Kingdom.
6
Division of B Cell Immunology, German Cancer Research Center, Heidelberg, Germany.
7
Department of Experimental Medicine, University of Genoa, Genoa, Italy.
8
BISC Global Inc., Boston, MA, United States.
9
Immunology Division, The Garvan Institute of Medical Research, Darlinghurst, NSW, Australia.
10
Fred Hutchinson Cancer Research Center, Seattle, WA, United States.
11
Vaccine Research Center, National Institutes of Health, Washington, DC, United States.
12
Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, BC, Canada.
13
Department of Biological Sciences, Simon Fraser University, Burnaby, BC, Canada.
14
Department of Molecular Biology and Biochemistry, Faculty of Health Sciences, Simon Fraser University, Burnaby, BC, Canada.
15
Department of Immunology, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
16
Faculty of Engineering, Bar Ilan University, Ramat Gan, Israel.
17
Department of Pathology, Yale University, New Haven, CT, United States.
18
Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, TX, United States.
19
Innovation Center for Law and Technology, New York Law School, New York, NY, United States.
20
IMGT®, The International ImMunoGenetics information system® (IMGT), Laboratoire d'ImmunoGénétique Moléculaire (LIGM), CNRS, Institut de Génétique Humaine, Université de Montpellier, Montpellier, France.
21
Department of Immunology and Pathology, Central Clinical School, The Alfred Hospital, Monash University, Melbourne, VIC, Australia.
22
Department of Biochemistry and Molecular Genetics, University of Louisville, Louisville, KY, United States.
23
School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW, Australia.

Abstract

Immunoglobulins or antibodies are the main effector molecules of the B-cell lineage and are encoded by hundreds of variable (V), diversity (D), and joining (J) germline genes, which recombine to generate enormous IG diversity. Recently, high-throughput adaptive immune receptor repertoire sequencing (AIRR-seq) of recombined V-(D)-J genes has offered unprecedented insights into the dynamics of IG repertoires in health and disease. Faithful biological interpretation of AIRR-seq studies depends upon the annotation of raw AIRR-seq data, using reference germline gene databases to identify the germline genes within each rearrangement. Existing reference databases are incomplete, as shown by recent AIRR-seq studies that have inferred the existence of many previously unreported polymorphisms. Completing the documentation of genetic variation in germline gene databases is therefore of crucial importance. Lymphocyte receptor genes and alleles are currently assigned by the Immunoglobulins, T cell Receptors and Major Histocompatibility Nomenclature Subcommittee of the International Union of Immunological Societies (IUIS) and managed in IMGT®, the international ImMunoGeneTics information system® (IMGT). In 2017, the IMGT Group reached agreement with a group of AIRR-seq researchers on the principles of a streamlined process for identifying and naming inferred allelic sequences, for their incorporation into IMGT®. These researchers represented the AIRR Community, a network of over 300 researchers whose objective is to promote all aspects of immunoglobulin and T-cell receptor repertoire studies, including the standardization of experimental and computational aspects of AIRR-seq data generation and analysis. The Inferred Allele Review Committee (IARC) was established by the AIRR Community to devise policies, criteria, and procedures to perform this function. Formalized evaluations of novel inferred sequences have now begun and submissions are invited via a new dedicated portal (https://ogrdb.airr-community.org). Here, we summarize recommendations developed by the IARC-focusing, to begin with, on human IGHV genes-with the goal of facilitating the acceptance of inferred allelic variants of germline IGHV genes. We believe that this initiative will improve the quality of AIRR-seq studies by facilitating the description of human IG germline gene variation, and that in time, it will expand to the documentation of TR and IG genes in many vertebrate species.

KEYWORDS:

AIRR-seq; IGHV; V(D)J rearrangement; allelic variation; immunoglobulin; inference

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