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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Immunol. | doi: 10.3389/fimmu.2018.02378

Antibody epitope specificity for dsDNA phosphate backbone is an intrinsic property of the heavy chain variable germline gene segment used.

  • 1Institute of Oncology and Radiology of Serbia, Serbia
  • 2Department of Microbiology, Immunology, and Molecular Genetics, University of Kentucky College of Medicine, United States
  • 3Faculty of Medical Sciences, University of Kragujevac, Serbia
  • 4Vinča Nuclear Institute, University of Belgrade, Serbia

Analysis of protein sequences by the informational spectrum method (ISM) enables characterization of their specificity according to encoded information represented with defined frequency (F). Our previous data showed that F(0.367) is characteristic for variable heavy chain (VH) domains (a combination of variable (V), diversity (D) and joining (J) gene segments) of the anti-phosphocholine (PC) T15 antibodies and mostly dependent on the CDR2 region, a site for PC phosphate group binding. Because the T15 dsDNA-reactive U4 mutant also encodes F(0.367), we hypothesized that the same frequency may also be characteristic for anti-DNA antibodies. Data obtained from an analysis of 60 spontaneously produced anti-DNA antibody VH domain sequences supported our hypothesis only for antibodies, which use V gene segment in germline configuration, such as S57(VH31), MRL-DNA22, and VH11, members of the VH1 (J558) and VH7 (S107) gene families. The important finding is that out of seven V gene segments used by spontaneous anti-DNA antibodies, F(0.367) is only expressed by the germline configuration of these three V gene segments. The data suggest that antibody specificity for the phosphate group moiety delineated as F(0.367) is the intrinsic property of the V germline gene segments used, whereas paratope/epitope interaction with antigens bearing this epitope, such as PC or dsDNA, requires corresponding antibody VH conformation that is susceptible to somatic mutation(s).

Keywords: anti-DNA antibodies, anti-PC antibodies, VH germline genes, dsDNA reactive antibodies, Characterization of antibody specificity by ISM

Received: 16 Aug 2018; Accepted: 25 Sep 2018.

Edited by:

Guido Ferrari, Duke University, United States

Reviewed by:

Cordula M. Stover, University of Leicester, United Kingdom
Gunnar Houen, State Serum Institute (SSI), Denmark  

Copyright: © 2018 Srdic-Rajic, Kohler, Jurisic and Metlas. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Radmila Metlas, Vinča Nuclear Institute, University of Belgrade, Belgrade, 11001, Serbia, metlas.r@sbb.rs