Véronique Giudicelli

Cancer remains one of the leading causes of mortality worldwide, accounting for approximately 9.7 million deaths in 2022. Faced with this significant publi

Over thousands of years, selective breeding of domestic dogs (Canis lupus familiaris) has led to extensive genetic diversity, underscoring the need for refined genomic and immunogenetic investigations. This study presents a comprehensive analysis and biocuration of the immunoglobulin kappa light chain locus (IGK) across multiple dog breeds to identify breed-specific variations and assess their relevance to canine immunology and veterinary diagnostics. We examined nine canine genome assemblies to characterize structural variations, polymorphisms, and gene diversity, with the goal of enriching the IMGT® reference database and expanding its representativeness across breeds. Through in-depth annotation of seven breeds—Bernese Mountain Dog, Boxer, Cairn Terrier, Labrador Retriever, Great Dane, Basenji, and German Shepherd—we identified 40 genes and 97 alleles, highlighting both conserved regions and unique breed-specific variants. Variants were validated in silico against Sanger sequencing data. Importantly, discrepancies were observed in the CanFam3.1 Boxer reference genome, indicating possible sequencing or assembly artifacts, challenges in gene and allele nomenclature standardization, and a low-density genomic segment within the IGK locus. These findings refine current knowledge of IGK locus diversity and enhance IMGT® database accuracy, supporting future studies on immunogenetic variability, somatic hypermutation, and immune response mechanisms in canine health and disease.

Monoclonal antibodies (mAbs) and fusion proteins for immune applications (FPIA) play a crucial role in treating autoimmune diseases and cancers by targeting cell-surface proteins and triggering multiple immune mechanisms. These functions are mediated by the crystallizable fragment (Fc) region of mAbs and fusion proteins, whose interaction with Fc gamma receptors (FcγRs) can be modulated through Fc amino acid (AA) engineering. To aid research in this area, we developed the IMGT/FcVariantsExplorer tool (https://www.imgt.org/fcvariantsexplorer/) to identify engineered AA changes or variants within the Fc region in mAb and fusion proteins sequences from IMGT/2Dstructure-DB, the AA sequence database of IMGT®, the international ImMunoGeneTics information system®. We used the IMGT® nomenclature of engineered Fc variants involved in antibody effector properties and formats, applying a standardized classification in five categories: 'Effector,' 'Half-life,' 'Physicochemical properties,' 'Structure,' and 'Hybrid.' We analyzed sequences from 1,107 mAbs and fusion proteins, identifying 483 entries with Fc AA changes, resulting in 211 unique Fc variants in the dataset. We also used web scraping to retrieve associated biological data from literature. All data have been integrated into IMGT/mAb-DB, with links to sequences in IMGT/2Dstructure-DB, enabling users to query Fc variants by their 'Category' or 'Effect.' This curated dataset reveals key trends in antibody engineering.

Antibodies, or immunoglobulins (IG), are central to the vertebrate adaptive immune system, yet the genomic architecture of IG loci remains poorly characterized in many nonhuman primates. In this study we present the first comprehensive genomic analysis of the immunoglobulin (IG) loci (IGH, IGL, and IGK) in two critically endangered orangutan species; Pongo abelii (Sumatran orangutan) and Pongo pygmaeus (Bornean orangutan) across multiple genome assemblies. Using IMGT-standardized biocuration framework combined with read-level structural validation, we identified previously undocumented haplotype-specific variation, including multigene duplications, asymmetric gene absence, and species-specific expansions of variable gene families. Recombination signal sequence (RSS) and switch region analyses revealed conserved regulatory motifs with potential implications for V(D)J recombination and class-switch recombination. These findings underscore the complexity and evolutionary adaptability of IG loci in great apes and highlight the value of orangutans as key references for understanding immune system evolution in the Hominidae lineage.

IMGT®, the international ImMunoGeneTics information system®, has advanced its comprehensive platform for the analysis of immunoglobulin (IG) and T-cell receptor (TR) genes through the development of new automated and scalable tools. This article presents major updates aligned with IMGT’s three axes of research. Axis I introduces dynamic resources such as IMGT/GeneTables, IMGT/AssemblyComparison, IMGT/CDRLengths, IMGT/MultiGenomeViewer, enabling real-time access to annotated genomic data, and IMGT/StatAssembly to assess quality of IG/TR loci in assemblies. Axis II enhances repertoire analysis with a redesigned IMGT/GeneFrequency tool and new customization features in IMGT/V-QUEST, supporting flexible exploration of IG and TR gene expression. Axis III improves the accurate prediction of peptide–MHC thanks to IMGT/RobustpMHC. Additionally, the IMGT knowledge graph and its therapeutic extension, IMGT/mAb-KG, provide semantically structured access to >100 million immunogenetic triplets, integrating IMGT databases and linking IMGT content to external biomedical resources. These developments promote standardization, interoperability, and integrative analysis across immunogenetics and clinical applications, reinforcing IMGT’s (accessible at https://www.imgt.org) role as a core reference in the era of FAIR data and personalized medicine.

The human immunoglobulin light chain loci, kappa (IGK) and lambda (IGL), are structurally complex genomic regions with germline gene content that is not yet fully characterized. These loci are marked by extensive gene duplication, allelic diversity, and segmental duplications, features that contribute critically to the adaptive immune response. In this study, we present a comprehensive IMGT annotation of IGK and IGL using two high-quality human reference assemblies (GRCh38 and T2T-CHM13) along with 142 and 125 additional chromosomal-level haploid assemblies, respectively for each locus, from individuals representing all major human superpopulations. Detailed gene and allele annotation of the reference assemblies led to the identification of 5 novel IGKV genes and 8 new IGKV alleles, 16 new IGLV genes, and 22 novel IGLV alleles. These were confirmed through assembly read validation, presence in whole genome sequencing datasets, and recurrence in multiple assemblies. Gene-level identification across the broader dataset enabled assessment of structural variation (SV) at both loci. IGL displayed high conservation, with recurrent absence observed for only one gene. In contrast, IGK exhibited greater variability, including complete loss of the distal region in certain assemblies. This structural diversity was analyzed across superpopulations, allowing us to map potential patterns of gene presence and absence across different ancestral groups. All newly identified genes were consistently observed across individuals and genomic backgrounds. This work enhances the structural resolution of the IGK and IGL loci and expands the IMGT reference directory with newly described germline genes and alleles. The results provide a more complete view of light chain genomic diversity and serve as a valuable resource for studies of antibody gene repertoires, immunogenetic variation, monoclonal antibody development and population-level diversity.

Background: Cancer remains one of the leading causes of mortality world-wide, accounting for approximately 9.7 million deaths in 2022. Faced with this significant public health challenge, therapeutic monoclonal antibodies (mAbs) have emerged as promising alternatives that may minimize the side effects associated with conventional treatments such as radiotherapy and chemotherapy. To support mAb research and development, IMGT®, the international ImMuno-GeneTics information system, has established two standardized data sources namely IMGT/mAb-DB, a comprehensive database for mAbs, and, more recently, IMGT/mAb-KG, a dedicated knowledge graph for mAbs. Despite these advances, the development of therapeutic mAbs remains both time-consuming and financially burdensome—costs can reach up to $2.8 billion. To address this challenge and accelerate cancer treatment, mAb repurposing represents a promising alternative. Results: In this study, we leveraged a subset of IMGT/mAb-KG, dedicated to the oncology domain, to develop a scientific hypothesis generation application for mAb repurposing. This application, based on knowledge graph embedding techniques, is designed to suggest potential mAb candidates for novel oncology applications. A user-friendly web interface provides access to the tool, incorporating visual support to facilitate the interpretation of generated hypotheses. This application is a decision support tool aiming to accelerate the discovery of new therapeutic applications for existing mAbs. Conclusion: Our application demonstrates the potential of knowledge graph embedding techniques in the oncology domain by enabling the repurposing of existing mAbs for new therapeutic uses. Using this tool, we have identified two novel mAbs, loncastuximab tesirine and glofitamab, both currently undergoing clinical trials for the treatment of chronic lymphocytic leukemia. This decision-support tool thus facilitates the discovery of new therapeutic opportunities by effectively repositioning existing mAbs for oncological indications, potentially accelerating the development of cancer therapies and addressing critical public health needs.

Monoclonal antibodies (mAbs) and fusion proteins for immune applications (FPIA) play a crucial role in treating autoimmune diseases and cancers by targeting cell-surface proteins and triggering multiple immune mechanisms. These functions are mediated by the fragment crystallizable (Fc) region of mAbs and fusion proteins, whose interaction with Fc gamma receptors (FcγRs) can be modulated through Fc amino acid (AA) engineering. To address this, we developed the IMGT/FcVariantsExplorer tool ( https://www.imgt.org/fcvariantsexplorer/ ) to identify AA changes within the Fc region in mAb and fusion proteins sequences from IMGT/2Dstructure-DB, the AA sequence database of IMGT®, the international ImMunoGeneTics information system®. We used the IMGT® nomenclature of engineered Fc variants involved in antibody effector properties and formats, applying a standardized classification in five categories: ‘Effector’, ‘Half-life’, ‘Physicochemical properties’, ‘Structure’, and ‘Hybrid’. We analyzed sequences of 1,107 mAbs and fusion proteins, identifying 483 entries with Fc AA changes, resulting in 211 unique Fc variants in the dataset. We also used web scraping to retrieve associated biological data from literature. All data have been integrated into IMGT/mAb-DB, with links to sequences in IMGT/2Dstructure-DB, enabling users to query Fc variants by their ‘Category’ or ‘Effect’. This curated dataset reveals key trends in antibody engineering.

IMGT®, the international ImMunoGeneTics information system®, has advanced its comprehensive platform for the analysis of immunoglobulin (IG) and T cell receptor (TR) genes through the development of new automated and scalable tools. This article presents major updates aligned with IMGT’s three axes of research. Axis I introduces dynamic resources such as IMGT/GeneTables, IMGT/AssemblyComparison, and IMGT/StatAssembly, enabling real-time access to annotated genomic data and quality assessment of assemblies. Axis II enhances repertoire analysis with a redesigned IMGT/GeneFrequency tool and new customization features in IMGT/V-QUEST, supporting flexible exploration of IG and TR gene expression. Axis III improves the accurate prediction of peptide-MHC thanks to IMGT/RobustpMHC. Additionally, the IMGT Knowledge Graph (IMGT-KG) and its therapeutic extension, IMGT/mAb-KG, provide semantically structured access to more than 100 million immunogenetic triplets, integrating IMGT databases and linking IMGT content to external biomedical resources. These developments promote standardization, interoperability, and integrative analysis across immunogenetics and clinical applications, reinforcing IMGT’s role as a core reference in the era of FAIR data and personalized medicine.