Comparative analysis of human and mouse immunoglobulin variable heavy regions from IMGT/LIGM-DB with IMGT/HighV-QUEST. 2014

Bin Shi, and Long Ma, and Xiaoyan He, and Xiaomei Wang, and Peng Wang, and Li Zhou, and Xinsheng Yao

BACKGROUND Immunoglobulin (IG) complementarity determining region (CDR) includes VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2 and VL CDR3. Of these, VH CDR3 plays a dominant role in recognizing and binding antigens. Three major mechanisms are involved in the formation of the VH repertoire: germline gene rearrangement, junctional diversity and somatic hypermutation. Features of the generation mechanisms of VH repertoire in humans and mice share similarities while VH CDR3 amino acid (AA) composition differs. Previous studies have mainly focused on germline gene rearrangement and the composition and structure of the CDR3 AA in humans and mice. However the number of AA changes due to somatic hypermutation and analysis of the junctional mechanism have been ignored. METHODS Here we analyzed 9,340 human and 6,657 murine unique productive sequences of immunoglobulin (IG) variable heavy (VH) domains derived from IMGT/LIGM-DB database to understand how VH CDR3 AA compositions significantly differed between human and mouse. These sequences were identified and analyzed by IMGT/HighV-QUEST (http://www.imgt.org), including gene usage, number of AA changes due to somatic hypermutation, AA length distribution of VH CDR3, AA composition, and junctional diversity. RESULTS Analyses of human and murine IG repertoires showed significant differences. A higher number of AA changes due to somatic hypermutation and more abundant N-region addition were found in human compared to mouse, which might be an important factor leading to differences in VH CDR3 amino acid composition. CONCLUSIONS These findings are a benchmark for understanding VH repertoires and can be used to characterize the VH repertoire during immune responses. The study will allow standardized comparison for high throughput results obtained by IMGT/HighV-QUEST, the reference portal for NGS repertoire.

UI MeSH Term Description Entries
D007135 Immunoglobulin Variable Region That region of the immunoglobulin molecule that varies in its amino acid sequence and composition, and comprises the binding site for a specific antigen. It is located at the N-terminus of the Fab fragment of the immunoglobulin. It includes hypervariable regions (COMPLEMENTARITY DETERMINING REGIONS) and framework regions. Variable Region, Ig,Variable Region, Immunoglobulin,Framework Region, Immunoglobulin,Fv Antibody Fragments,Fv Fragments,Ig Framework Region,Ig Variable Region,Immunoglobulin Framework Region,Immunoglobulin Fv Fragments,Immunoglobulin V,Antibody Fragment, Fv,Antibody Fragments, Fv,Fragment, Fv,Fragment, Fv Antibody,Fragment, Immunoglobulin Fv,Fragments, Fv,Fragments, Fv Antibody,Fragments, Immunoglobulin Fv,Framework Region, Ig,Framework Regions, Ig,Framework Regions, Immunoglobulin,Fv Antibody Fragment,Fv Fragment,Fv Fragment, Immunoglobulin,Fv Fragments, Immunoglobulin,Ig Framework Regions,Ig Variable Regions,Immunoglobulin Framework Regions,Immunoglobulin Fv Fragment,Immunoglobulin Variable Regions,Regions, Immunoglobulin Variable,Variable Regions, Ig,Variable Regions, Immunoglobulin
D007143 Immunoglobulin Heavy Chains The largest of polypeptide chains comprising immunoglobulins. They contain 450 to 600 amino acid residues per chain, and have molecular weights of 51-72 kDa. Immunoglobulins, Heavy-Chain,Heavy-Chain Immunoglobulins,Ig Heavy Chains,Immunoglobulin Heavy Chain,Immunoglobulin Heavy Chain Subgroup VH-I,Immunoglobulin Heavy Chain Subgroup VH-III,Heavy Chain Immunoglobulins,Heavy Chain, Immunoglobulin,Heavy Chains, Ig,Heavy Chains, Immunoglobulin,Immunoglobulin Heavy Chain Subgroup VH I,Immunoglobulin Heavy Chain Subgroup VH III,Immunoglobulins, Heavy Chain
D009154 Mutation Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations. Mutations
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000595 Amino Acid Sequence The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION. Protein Structure, Primary,Amino Acid Sequences,Sequence, Amino Acid,Sequences, Amino Acid,Primary Protein Structure,Primary Protein Structures,Protein Structures, Primary,Structure, Primary Protein,Structures, Primary Protein
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001483 Base Sequence The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence. DNA Sequence,Nucleotide Sequence,RNA Sequence,DNA Sequences,Base Sequences,Nucleotide Sequences,RNA Sequences,Sequence, Base,Sequence, DNA,Sequence, Nucleotide,Sequence, RNA,Sequences, Base,Sequences, DNA,Sequences, Nucleotide,Sequences, RNA
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus

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