T cells of lupus and molecular targets for immunotherapy

Syamal K. Datta*, Arunan Kaliyaperumal, Ami Desai-Mehta

*Corresponding author for this work

Research output: Contribution to journalReview article

22 Scopus citations

Abstract

A major advance in understanding the basic mechanism driving the pathogenic autoimmune response in SLE has been the identification of nucleosome as a primary immunogen. The production of pathogenic antinuclear antibodies in SLE is mediated by a MHC class II restricted, cognate interaction between select populations of autoimmune T helper cells and autoimmune B cells that recognize epitopes in the different molecular components of the nucleosome particle: a form of intermolecular-intrastructural help. In the SNF1 model, 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 H-2B 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 B cells, as well as the sites where the histones contact DNA in the nucleosome, indicating that they are specially protected during antigen processing. Identification of the peptide epitopes is a basic step toward defining how the pathogenic Th cells emerge in lupus. In addition, we found that the pathogenic Th cells and B cells of lupus have a regulatory defect in the expression of CD40 ligand (CD40L or gp39), which results in abnormal costimulatory signals that sustain the production of pathogenic autoantibodies. Specific immunotherapy that blocks the pathogenic T and B cell interaction in lupus can be designed based on the knowledge of these disease mechanisms.

Original languageEnglish (US)
Pages (from-to)11-20
Number of pages10
JournalJournal of Clinical Immunology
Volume17
Issue number1
DOIs
Publication statusPublished - Feb 28 1997

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Keywords

  • CD40 ligand
  • T cell receptors
  • anti-DNA autoantibody
  • autoimmune disease
  • immunotherapy
  • nucleosomal epitopes
  • systemic lupus erythematosus

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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