Next-generation sequencing reveals new insights about gene usage and CDR-H3 composition in the horse antibody repertoire

Mol Immunol. 2019 Jan:105:251-259. doi: 10.1016/j.molimm.2018.11.017. Epub 2018 Dec 15.

Abstract

Horse serum antibodies have been used for greater than a century for the treatment and prophylaxis of infectious diseases and envenomations. Little is known, however, about the immunogenetic diversity that produces horse serum antibodies. Here, we employed next-generation sequencing for a first-in-kind comprehensive analysis of the equine B-cell repertoire. Nearly 45,000 and 30,000 clonotypes were obtained for the heavy-chain (IGH) and lambda light-chain (IGL) loci, respectively. We observed skewed use of the common subgroups IGHV2 (92.49%) and IGLV8 (82.50%), consistent with previous reports, but also novel use of the rare genes IGHV6S1 and IGLV4S2. CDR-H3 amino acid composition revealed different amino acid patterns at positions 106 and 116 compared to human, rabbit, and mouse, suggesting that an extended conformation predominates among horse CDR-H3 loops. Our analysis provides new insights regarding the mechanisms employed to generate antibody diversity in the horse, and could be applicable to the optimized design of synthetic antibodies intended for future therapeutic use.

Keywords: Antibody repertoire; CDR-H3 composition; Diversity; Horse; Immunoglobulin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Complementarity Determining Regions / genetics*
  • Complementarity Determining Regions / immunology
  • Genetic Loci*
  • High-Throughput Nucleotide Sequencing*
  • Horses / genetics*
  • Horses / immunology
  • Humans
  • Immunoglobulin Heavy Chains / genetics*
  • Immunoglobulin Heavy Chains / immunology
  • Immunoglobulin lambda-Chains / genetics*
  • Immunoglobulin lambda-Chains / immunology
  • Mice
  • Rabbits

Substances

  • Complementarity Determining Regions
  • Immunoglobulin Heavy Chains
  • Immunoglobulin lambda-Chains