title: Comparative analysis of human and mouse immunoglobulin variable heavy regions from IMGT/LIGM-DB with IMGT/HighV-QUEST.
abstract: 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.
authors.forename: Bin
authors.initials: B
authors.lastname: Shi
authors.forename: Long
authors.initials: L
authors.lastname: Ma
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: He
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Wang
authors.forename: Peng
authors.initials: P
authors.lastname: Wang
authors.forename: Li
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Department of Immunology, Research Center for Medicine & Biology, Innovation & Practice Base for Graduate Students Education, Zunyi Medical University, Zunyi 563000, China. immunology01@126.com.
authors.forename: Xinsheng
authors.initials: X
authors.lastname: Yao
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000737:chemistry* / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000737:chemistry* / Q000235:genetics; D051379:Mice; D009154:Mutation
chemical_list: D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region