TCR peptide therapy in human autoimmune diseases

Arthur A. Vandenbark, Elizabeth Morgan, Richard Bartholomew, Dennis Bourdette, Ruth Whitham, Dennis Carlo, Daniel Gold, George Hashim, Halina Offner

Research output: Contribution to journalArticlepeer-review

48 Scopus citations


Inflammatory Th1 cells reacting to tissue/myelin derived antigens likely contribute to the pathogenesis of diseases such as multiple sclerosis (MS), rheumatoid arthritis (RA), and psoriasis. One regulatory mechanism that may be useful for treating autoimmune diseases involves an innate second set of Th2 cells specific for portions of the T cell receptor of clonally expanded pathogenic Th1 cells. These Th2 cells are programmed to respond to internally modified V region peptides from the T cell receptor (TCR) that are expressed on the Th1 cell surface in association with major histocompatibility molecules. Once the regulatory Th2 cells are specifically activated, they may inhibit inflammatory Th1 cells through a non-specific bystander mechanism. A variety of strategies have been used by us to identify candidate disease-associated TCR V genes present on pathogenic Th1 cells, including BV5S2, BV6S5, and BV13S1 in MS, BV3, BV14, and BV17 in RA, and BV3 and BV13S1 in psoriasis. TCR peptides corresponding to the mid region of these BV genes were found to be consistently immunogenic in vivo when administered either i.d. in saline or i.m. in incomplete Freund's adjuvant (IFA). In MS patients, repeated injection of low doses of peptides (100-300 μg) significantly boosted the number of TCR-reactive Th2 cells. These activated cells secreted cytokines, including IL-10, that are known to inhibit inflammatory Th1 cells. Cytokine release could also be induced in TCR-reactive Th2 cells by direct cell-cell contact with Th1 cells expressing the target V gene. These findings indicate the potential of regulatory Th2 cells to inhibit not only the target Th1 cells, but also bystander Th1 cells expressing different V genes specific for other autoantigens. TCR peptide vaccines have been used in our studies to treat a total of 171 MS patients (6 trials), 484 RA patients (7 trials), and 177 psoriasis patients (2 trials). Based on this experience in 824 patients with autoimmune diseases, TCR peptide vaccination is safe and well tolerated, and can produce significant clinical improvement in a subset of patients that respond to immunization. TCR peptide vaccination represents a promising approach that is well-suited for treating complex autoimmune diseases.

Original languageEnglish (US)
Pages (from-to)713-730
Number of pages18
JournalNeurochemical Research
Issue number6
StatePublished - 2001


  • Autoimmune diseases
  • Immunotherapy
  • Regulatory cytokines
  • T cell receptor

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience


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