Recombinant T cell receptor ligands: immunomodulatory, neuroprotective and neuroregenerative effects suggest application as therapy for multiple sclerosis.
Recombinant T cell receptor (TCR) ligands (RTL) represent the minimal interactive surface with antigen-specific T cell receptors. These novel constructs fold similarly to native four-domain MHC/peptide complexes but deliver suboptimal and qualitatively different signals that cause a 'cytokine switch' to anti-inflammatory factors in targeted encephalitogenic T cells. RTL treatment can reverse clinical and histological signs of experimental autoimmune encephalomyelitis (EAE) and most dramatically can promote myelin and axonal recoveiy in the CNS of mice with chronic disease. These properties of RTL suggest that this novel antigen-specific approach may hold unusual promise as a therapy for multiple sclerosis.
Offner
Halina
H
Neuroimmunology Research, Veterans Affairs Medical Center, Portland, OR 97239, USA. offnerva@ohsu.edu
Sinha
Sushmita
S
Wang
Chunhe
C
Burrows
Gregory G
GG
Vandenbark
Arthur A
AA
D000818:Animals; D004195:Disease Models, Animal; D006801:Humans; D008024:Ligands; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D009416:Nerve Regeneration / Q000187:drug effects*; D011948:Receptors, Antigen, T-Cell / Q000187:drug effects*; D011993:Recombinant Fusion Proteins / Q000276:immunology* / Q000627:therapeutic use
D008024:Ligands; D011948:Receptors, Antigen, T-Cell; D011993:Recombinant Fusion Proteins