Analysis of 5518 unique, productively rearranged human VH3-23*01 gene sequences reveals CDR-H3 length-dependent usage of the IGHD2 gene family

Protein Eng Des Sel. 2017 Sep 1;30(9):603-609. doi: 10.1093/protein/gzx027.

Abstract

Clear and accurate understanding of diversity in antibody complementarity-determining regions (CDRs) is critical for antibody discovery and engineering. Previous observations of antibody CDR-H3 diversity were based on analyzing available antibody sequences in the public databases. The results may not accurately reflect that of natural antibody repertoire due to erroneous species annotation and the presence of man-made CDR loop diversity in public antibody sequence databases. In this study, in a precisely controlled germline context, we explored the relationship between amino acid composition and CDR-H3 length using 5518 unique productively rearranged human VH3-23*01 gene sequences. CDR-H3 length-dependent usage of the Cys-Xn-Cys motif is reported here.

Keywords: IGHD2; VH3-23*01.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Antibodies / chemistry*
  • Antibodies / genetics
  • Antibody Diversity
  • Complementarity Determining Regions / chemistry*
  • Complementarity Determining Regions / genetics
  • Cysteine / chemistry*
  • Cysteine / immunology
  • Databases, Protein
  • Gene Expression
  • Humans
  • Immunoglobulin Variable Region / chemistry*
  • Immunoglobulin Variable Region / genetics
  • Models, Molecular
  • Protein Structure, Secondary

Substances

  • Antibodies
  • Complementarity Determining Regions
  • Immunoglobulin Variable Region
  • Cysteine