Systemic immunomodulation of autoimmune disease using MHC-derived recombinant TCR ligands

Gregory G. Burrows

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Human autoimmune disease involves local activation of antigen-specific CD4+ T cells that produce inflammatory Th1 cytokines leading to the further recruitment and activation of lymphocytes and monocytes, resulting ultimately in the destruction of target tissue. Antigen presenting cells (APCs) initiate activation of CD4+ T cells in a multistep process that minimally involves co-ligation of the TCR and CD4 by the MHC class II/peptide complex and costimulation through additional T cell surface molecules such as CD28. Disruption of this highly orchestrated series of events can result in the direct modulation of CD4+ T cell behavior. The interaction between MHC and TCR holds unique promise as a focal point for therapeutic intervention in the pathology of CD4+ T cell-mediated diseases, and MHC class II-derived Recombinant TCR Ligands ("RTLs") have emerged as a new class of therapeutics with potent clinical efficacy in a diverse set of animal models for multiple sclerosis. Here I review the systemic effect that RTL therapy has on the intact immune system and present an overview of a molecular mechanism by which RTL therapy could induce these systemic changes.

Original languageEnglish (US)
Pages (from-to)185-193
Number of pages9
JournalCurrent Drug Targets: Inflammation and Allergy
Volume4
Issue number2
DOIs
StatePublished - Apr 2005

Fingerprint

Immunomodulation
Autoimmune Diseases
Ligands
T-Lymphocytes
CD4 Antigens
Antigen-Presenting Cells
Therapeutics
Lymphocyte Activation
Multiple Sclerosis
Ligation
Monocytes
Immune System
Animal Models
Pathology
Cytokines
Peptides

Keywords

  • EAE
  • Immunoregulation
  • MHC/peptides
  • Multiple sclerosis
  • Recombinant TCR ligand
  • T cell receptor
  • T lymphocytes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Pharmacology
  • Immunology

Cite this

Systemic immunomodulation of autoimmune disease using MHC-derived recombinant TCR ligands. / Burrows, Gregory G.

In: Current Drug Targets: Inflammation and Allergy, Vol. 4, No. 2, 04.2005, p. 185-193.

Research output: Contribution to journalArticle

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