title: Comparative analysis of the feline immunoglobulin repertoire.
abstract: Next-Generation Sequencing combined with bioinformatics is a powerful tool for analyzing the large number of DNA sequences present in the expressed antibody repertoire and these data sets can be used to advance a number of research areas including antibody discovery and engineering. The accurate measurement of the immune repertoire sequence composition, diversity and abundance is important for understanding the repertoire response in infections, vaccinations and cancer immunology and could also be useful for elucidating novel molecular targets. In this study 4 individual domestic cats (Felis catus) were subjected to antibody repertoire sequencing with total number of sequences generated 1079863 for VH for IgG, 1050824 VH for IgM, 569518 for VK and 450195 for VL. Our analysis suggests that a similar VDJ expression patterns exists across all cats. Similar to the canine repertoire, the feline repertoire is dominated by a single subgroup, namely VH3. The antibody paratope of felines showed similar amino acid variation when compared to human, mouse and canine counterparts. All animals show a similarly skewed VH CDR-H3 profile and, when compared to canine, human and mouse, distinct differences are observed. Our study represents the first attempt to characterize sequence diversity in the expressed feline antibody repertoire and this demonstrates the utility of using NGS to elucidate entire antibody repertoires from individual animals. These data provide significant insight into understanding the feline immune system function.
authors.affiliation: Zoetis VMRD Global Therapeutics Research, 333 Portage Street, Kalamazoo, MI 49001, USA. Electronic address: sebastian.steiniger@zoetis.com.
authors.forename: Sebastian C J
authors.initials: SC
authors.lastname: Steiniger
authors.affiliation: Distributed Bio Inc, San Francisco, CA, USA.
authors.forename: Jacob
authors.initials: J
authors.lastname: Glanville
authors.affiliation: Zoetis VMRD Global Therapeutics Research, 333 Portage Street, Kalamazoo, MI 49001, USA.
authors.forename: Douglas W
authors.initials: DW
authors.lastname: Harris
authors.affiliation: Zoetis VMRD Global Therapeutics Research, 333 Portage Street, Kalamazoo, MI 49001, USA.
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Wilson
authors.affiliation: Department of Molecular Biosciences, University of Texas at Austin, Austin, TX, USA.
authors.forename: Gregory C
authors.initials: GC
authors.lastname: Ippolito
authors.affiliation: Zoetis VMRD Global Therapeutics Research, 333 Portage Street, Kalamazoo, MI 49001, USA.
authors.forename: Steven A
authors.initials: SA
authors.lastname: Dunham
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies / Q000235:genetics; D002415:Cats; D022801:Complementarity Determining Regions / Q000235:genetics; D004285:Dogs; D020869:Gene Expression Profiling / Q000379:methods; D014644:Genetic Variation; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007147:Immunoglobulin Light Chains / Q000235:genetics*; D051379:Mice; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050441:VDJ Exons / Q000235:genetics
chemical_list: D000906:Antibodies; D022801:Complementarity Determining Regions; D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains
keywords: Amino acid composition; Antibody engineering; Feline antibody repertoire; Immunoglobulin heavy chain complementary-determining region 3