IMGT® Biocuration and Analysis of the Rhesus Monkey IG Loci

Abstract

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.

Keywords: IGH locus; IGK locus; IGL locus; IMGT; Macaca mulatta; immunogenetics; immunoglobulins; immunoinformatics.

Figure 1

Locus representation of the Macaca mulatta (rhesus monkey) IGH deduced from the genome assembly Mmul_10. Reproduced with permission from IMGT^®, the international ImMunoGeneTics information system^®, http://www.imgt.org (accessed on 11 November 2021) The diagram shows the IGH genes and positions on the locus according to the IMGT nomenclature [1]. The arrows indicate an inverse transcriptional orientation in the locus. The V-D-J-C-CLUSTER is composed of IGHV(V6-1 to V(II)-202)-IGHD(D1-1 to D7-45)-IGHJ(J1 to J6)-IGHC(IGHM-IGHD-IGHG1-IGHG2-IGHG3-IGHG4-IGHE-IGHA). The 20 unlocalized V-GENE have a provisional nomenclature and are not present on the locus representation. Data available in IMGT Repertoire (IG and TR) http://www.imgt.org/IMGTrepertoire/, accessed on 11 November 2021 > Locus and genes > Locus representations > IGH > Rhesus monkey.

Figure 2

IMGT Protein display of the Macaca mulatta (rhesus monkey) IGHV genes. Only a few functional genes, ORF and in-frame P are shown as examples. The outline of the CDR-IMGT and FR-IMGT are according to the IMGT unique numbering for V-REGION [70]. The four conserved amino acids are shaded in pink for the C23 and C104, blue for the W41 and hydrophobic AA 89. * indicates in frame STOP-CODON. The CDR-IMGT are shaded in maroon while the FR-IMGT are in black. Data available in IMGT Repertoire (IG and TR) http://www.imgt.org/IMGTrepertoire/, accessed on 11 November 2021 > Proteins and alleles > Protein displays > V-DOMAIN > IGHV > Rhesus monkey (Macaca mulatta) or IMGT DomainDisplay http://www.imgt.org/3Dstructure-DB/cgi/DomainDisplay.cgi, accessed on 11 November 2021.

Figure 3

Recombination signal sequences of functional V, D and J genes (V-RS, 5′D-RS, 3′D-RS and J-RS respectively) for each IG locus of the rhesus monkey. The height of symbols indicates the relative frequency of each nucleotide at that position. Data extracted from IMGT Repertoire (IG and TR) http://www.imgt.org/genedb/, accessed on 11 November 2021 and depicted as sequence logos by WebLogo [71].

Figure 4

Schematic representation of the IGHV genes promoter organization per subgroup, based on the regulatory elements consensus sequences, positions and distances. Each element is represented by a specific color according to the IMGT color menu for the organization of the V-GENE promoters. The IMGT labels of each element are mentioned in parentheses in the legend.

Figure 5

Locus representation of the Macaca mulatta (rhesus monkey) IGL locus deduced from the genome assembly Mmul_10. Reproduced with permission from IMGT^®, the international ImMunoGeneTics information system^®, http://www.imgt.org, (accessed on 11 November 2021). A dotted line… indicates the distance in kb between the locus and the IMGT 3′ borne. A, B, C refer to three distinct V-CLUSTER based on the IGLV gene subgroup content, by homology with the Homo sapiens IGL locus. The IGL J-C-CLUSTER comprises 8 cassettes indicated by the numbers 1 to 7 (IGLJ1-IGLC1, IGLJ2-IGLC2, IGLJ2A-IGLC2A, IGLJ3-IGLC3, IGLJ4-IGLC4, IGLJ5-IGLC5, IGLJ6-IGLC6 and IGLJ7-IGLC7 respectively) (Supplementary Figure S1). The 22 unlocalized V-GENE have a provisional nomenclature and are not present on the locus representation. Data available in IMGT Repertoire (IG and TR) http://www.imgt.org/IMGTrepertoire/, accessed on 11 November 2021 > Locus and genes > Locus representations > IGL > Rhesus monkey.

Figure 6

IMGT Protein display of the Macaca mulatta (rhesus monkey) IGLV genes. Only a few functional genes, ORF and in-frame P are shown, as examples. The outline of the CDR-IMGT and FR-IMGT are according to the IMGT unique numbering for V-REGION [70]. The four conserved amino acids are shaded in pink for the C23 and C104, blue for the W41 and hydrophobic AA 89. * indicates in frame STOP-CODON. The CDR-IMGT are shaded in maroon while the FR-IMGT are in black. Data available in IMGT Repertoire (IG and TR) http://www.imgt.org/IMGTrepertoire/, accessed on 11 November 2021 > Proteins and alleles > Protein displays > V-DOMAIN > IGLV > Rhesus monkey (Macaca mulatta) or IMGT DomainDisplay http://www.imgt.org/3Dstructure-DB/cgi/DomainDisplay.cgi, accessed on 11 November 2021.

Figure 7

Schematic representation of the IGLV genes promoter organization per subgroup, based on the regulatory elements consensus sequences, positions and distances. Each element is represented by a specific color according to the IMGT color menu for the organization of the V-GENE promoters. The IMGT labels of each element are mentioned in parentheses in the legend.

Figure 8

Locus representation of the Macaca mulatta (rhesus monkey) IGK deduced from the genome assembly Mmul_10. Reproduced with permission from IMGT^®, the international ImMunoGeneTics information system^®, http://www.imgt.org (accessed on 11 November 2021). A dotted line… indicates the distance in kb between the locus and the IMGT 5′ borne. These distances are not represented at scale and are not included in the numbers displayed at the right ends of these two lines. IGKV2-13-1, IGKV2-13-2, IGKV1-25-1 and IGKV3-26-1 genes are not found in the Mmul_10 assembly (IMGT000063 accession number) but found in the accession number NW_001099007. Data available in IMGT Repertoire (IG and TR) http://www.imgt.org/IMGTrepertoire/, accessed on 11 November 2021 > Locus and genes > Locus representations > IGK > Rhesus monkey.

Figure 9

IMGT Protein display of the Rhesus monkey IGKV genes. Only a few functional genes, ORF and in-frame P are shown. The outline of complementarity determining regions (CDR-IMGT) and framework regions (FR-IMGT) are according to the IMGT unique numbering for V-REGION [70]. The four conserved amino acids are shaded in pink for the C23 and C104, blue for the W41 and hydrophobic AA 89. * indicates in frame STOP-CODON. The CDR-IMGT are shaded in maroon while the FR-IMGT are in black. Data available in IMGT Repertoire (IG and TR) http://www.imgt.org/IMGTrepertoire/, accessed on 11 November 2021 > Proteins and alleles > Protein displays > V-DOMAIN > IGKV > Rhesus monkey (Macaca mulatta) or IMGT DomainDisplay http://www.imgt.org/3Dstructure-DB/cgi/DomainDisplay.cgi, accessed on 11 November 2021.

Figure 10

Schematic representation of the IGKV genes promoter organization per subgroup, based on the regulatory elements consensus sequences, positions and distances. Each element is represented by a specific color according to the IMGT color menu for the organization of the V-GENE promoters. The IMGT labels of each element are mentioned in parentheses in the legend.