title: Antigen-specific blocking of CD4-specific immunological synapse formation using BPI and current therapies for autoimmune diseases.
abstract: In this review, we discuss T-cell activation, etiology, and the current therapies of autoimmune diseases (i.e., MS, T1D, and RA). T-cells are activated upon interaction with antigen-presenting cells (APC) followed by a "bull's eye"-like formation of the immunological synapse (IS) at the T-cell-APC interface. Although the various disease-modifying therapies developed so far have been shown to modulate the IS and thus help in the management of these diseases, they are also known to present some undesirable side effects. In this study, we describe a novel and selective way to suppress autoimmunity by using a bifunctional peptide inhibitor (BPI). BPI uses an intercellular adhesion molecule-1 (ICAM-1)-binding peptide to target antigenic peptides (e.g., proteolipid peptide, glutamic acid decarboxylase, and type II collagen) to the APC and therefore modulate the immune response. The central hypothesis is that BPI blocks the IS formation by simultaneously binding to major histocompatibility complex-II and ICAM-1 on the APC and selectively alters the activation of T cells from T(H)1 to T(reg) and/or T(H)2 phenotypes, leading to tolerance.
authors: Department of Pharmaceutical Chemistry, University of Kansas, Lawrence, KA 66047, USA.
authors: Prakash
authors: P
authors: Manikwar
authors: Paul
authors: P
authors: Kiptoo
authors: Ahmed H
authors: AH
authors: Badawi
authors: Barlas
authors: B
authors: Büyüktimkin
authors: Teruna J
authors: TJ
authors: Siahaan
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000378:metabolism; D001327:Autoimmune Diseases / Q000276:immunology* / Q000378:metabolism / Q000628:therapy; D015704:CD4 Antigens / Q000276:immunology* / Q000378:metabolism; D024043:Collagen Type II / Q000378:metabolism; D005968:Glutamate Decarboxylase / Q000378:metabolism; D006801:Humans; D054992:Immunological Synapses / Q000378:metabolism*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008954:Models, Biological; D010455:Peptides / Q000494:pharmacology / Q000627:therapeutic use; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
chemical_list: D015704:CD4 Antigens; D024043:Collagen Type II; D010455:Peptides; D018799:Intercellular Adhesion Molecule-1; D005968:Glutamate Decarboxylase