Self-Antigens Displayed on Liposomal Nanoparticles above a Threshold of Epitope Density Elicit Class-Switched Autoreactive Antibodies Independent of T Cell Help

J Immunol. 2020 Jan 15;204(2):335-347. doi: 10.4049/jimmunol.1801677. Epub 2019 Dec 13.


Epitope density has a profound impact on B cell responses to particulate Ags, the molecular mechanisms of which remain to be explored. To dissect the role of epitope density in this process, we have synthesized a series of liposomal particles, similar to the size of viruses, that display a model self-antigen peptide at defined surface densities. Immunization of C57BL/6J mice using these particles elicited both IgM and class-switched IgG1, IgG2b, and IgG3 autoreactive Abs that depended on the epitope density. In C57BL/6 gene knockout mice lacking either functional TCRs or MHC class II molecules on B cells, the liposomal particles also elicited IgM, IgG1, IgG2b, and IgG3 responses that were comparable in magnitudes to wild-type mice, suggesting that this B cell response was independent of cognate T cell help. Notably, the titer of the IgG in wild-type animals could be increased by more than 200-fold upon replacement of liposomes with bacteriophage Qβ virus-like particles that displayed the same self-antigen peptide at comparable epitope densities. This enhancement was lost almost completely in gene knockout mice lacking either TCRs or MHC class II molecules on B cells. In conclusion, epitope density above a threshold on particulate Ags can serve as a stand-alone signal to trigger secretion of autoreactive and class-switched IgG in vivo in the absence of cognate T cell help or any adjuvants. The extraordinary immunogenicity of Qβ viral-like particles relies, in large part, on their ability to effectively recruit T cell help after B cell activation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoantibodies / blood*
  • Autoantigens / immunology
  • Cells, Cultured
  • Cytokines / metabolism
  • Epitopes, B-Lymphocyte / metabolism
  • Immunoglobulin Class Switching
  • Immunoglobulin G / blood*
  • Liposomes / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Nanoparticles / metabolism
  • Peptides / immunology
  • T-Lymphocytes, Helper-Inducer / immunology*
  • Tumor Necrosis Factor-alpha / immunology
  • Virion / immunology


  • Autoantibodies
  • Autoantigens
  • Cytokines
  • Epitopes, B-Lymphocyte
  • Immunoglobulin G
  • Liposomes
  • Peptides
  • Tumor Necrosis Factor-alpha