Introduction

The adaptive immune system confers protection by generating a diverse repertoire of antibody receptors that are rapidly expanded and contracted in response to specific targets. Next-generation DNA sequencing now provides the opportunity to survey this complex and vast repertoire. In the present work, we describe a set of tools for the analysis of antibody repertoires and their application to elucidating the dynamics of the response to viral vaccination in human volunteers. By analyzing data from 38 separate blood samples across 2 y, we found that the use of the germ-line library of V and J segments is conserved between individuals over time. Surprisingly, there appeared to be no correlation between the use level of a particular VJ combination and degree of expansion. We found the antibody RNA repertoire in each volunteer to be highly dynamic, with each individual displaying qualitatively different response dynamics. By using combinatorial phage display, we screened selected VH genes paired with their corresponding VL library for affinity against the vaccine antigens. Altogether, this work presents an additional set of tools for profiling the human antibody repertoire and demonstrates characterization of the fast repertoire dynamics through time in multiple individuals responding to an immune challenge.

Publications

  1. High-resolution antibody dynamics of vaccine-induced immune responses.
    Cite this
    Laserson U, Vigneault F, Gadala-Maria D, Yaari G, Uduman M, Vander Heiden JA, Kelton W, Taek Jung S, Liu Y, Laserson J, Chari R, Lee JH, Bachelet I, Hickey B, Lieberman-Aiden E, Hanczaruk B, Simen BB, Egholm M, Koller D, Georgiou G, Kleinstein SH, Church GM, 2014-04-01 - Proceedings of the National Academy of Sciences of the United States of America

Credits

  1. Uri Laserson
    Developer

    Harvard-MIT Division of Health Sciences and Technology, Cambridge

  2. Francois Vigneault
    Developer

  3. Daniel Gadala-Maria
    Developer

  4. Gur Yaari
    Developer

  5. Mohamed Uduman
    Developer

  6. Jason A Vander Heiden
    Developer

  7. William Kelton
    Developer

  8. Sang Taek Jung
    Developer

  9. Yi Liu
    Developer

  10. Jonathan Laserson
    Developer

  11. Raj Chari
    Developer

  12. Je-Hyuk Lee
    Developer

  13. Ido Bachelet
    Developer

  14. Brendan Hickey
    Developer

  15. Erez Lieberman-Aiden
    Developer

  16. Bozena Hanczaruk
    Developer

  17. Birgitte B Simen
    Developer

  18. Michael Egholm
    Developer

  19. Daphne Koller
    Developer

  20. George Georgiou
    Developer

  21. Steven H Kleinstein
    Developer

  22. George M Church
    Investigator

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Summary
AccessionBT000103
Tool TypeApplication
Category
PlatformsLinux/Unix
Technologies
User InterfaceTerminal Command Line
Download Count0
Submitted ByGeorge M Church