12
Views
0
CrossRef citations to date
0
Altmetric
Review

Systemic lupus: basic mechanisms and prospects for specific immunotherapy

Pages 247-261 | Published online: 02 Jan 2014
 

Abstract

Nucleosomes are the primary immunogens that initiate the pathogenic autoimmune response in SLE. The production of pathogenic anti-nuclear antibodies in murine as well as human lupus is mediated by a MHC class-II restricted, cognate interaction between select populations of autoimmune T helper (Th) cells and autoimmune B cells that recognize epitopes in the different molecular components of the nucleosome particle. In the SNF1 model of lupus, we have localized the critical peptide autoepitopes for lupus nephritis-inducing Th cells in the core histones of nucleosomes, at amino acid positions 10–33 of H2B, and 16–39 and 71–94 of H4. Remarkably, the nephritogenic epitopes are located in the regions of histones that are also targeted by lupus autoantibodies, as well as the sites where the histones contact with DNA in the nucleosome, indicating that they are specially protected during antigen processing. The localization of the critical peptide autoepitopes in nucleosomes is a basic step towards defining how the pathogenic Th cells emerge in lupus. In addition, the pathogenic Th cells and B cells of lupus have a regulatory defect in the expression of CD40 ligand (CD40L or gp39), which mediates abnormal co-stimulatory signals sustaining the production of pathogenic autoantibodies. Immunotherapy that specifically blocks the pathogenic T and B cell interaction in lupus can be developed based on these studies.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.