Large-scale sequence and structural comparisons of human naive and antigen-experienced antibody repertoires

Abstract

We applied a very recently developed experimental strategy for high-throughput sequencing of paired antibody heavy and light chains along with large-scale computational structural modeling to delineate features of the human antibody repertoire at unprecedented scale. Comparison of antibody repertoires encoded by peripheral naive and memory B cells revealed ( i ) preferential enrichment or depletion of specific germline gene combinations for heavy- and light-chain variable regions and ( ii ) enhanced positive charges, higher solvent-accessible surface area, and greater hydrophobicity at antigen-binding regions of mature antibodies. The data presented in this report provide fundamental new insights regarding the biological features of antibody selection and maturation and establish a benchmark for future studies of antibody responses to disease or to vaccination.

Document Details

Document Type
Pub Defense Publication
Publication Date
Apr 25, 2016
Source ID
10.1073/pnas.1525510113

Entities

People

  • Andrew D Ellington
  • Brandon J DeKosky
  • Constantine Chrysostomou
  • Daechan Park
  • Daisuke Kuroda
  • Erik L. Johnson
  • George Georgiou
  • Gregory C Ippolito
  • Jeffrey J. Gray
  • Oana I. Lungu
  • Wissam Charab

Organizations

  • Defense Threat Reduction Agency
  • Hertz Foundation
  • Johns Hopkins University
  • National Institutes of Health
  • National Science Foundation
  • University of Texas at Austin

Tags

Fields of Study

  • Biology

Readers

  • Molecular and Cellular Biochemistry
  • Neural Network Machine Learning.
  • Oncology

Technology Areas

  • Biotechnology
  • Biotechnology - Cancer Biotech