Manipulating Antigenic Ligand Strength to Selectively Target Myelin-Reactive CD4+ T Cells in EAE

• Published in: Journal of neuroimmune pharmacology Vol. 5; no. 2; pp. 176 - 188
• Main Authors: Sabatino, Joseph J., Rosenthal, Kristen M., Evavold, Brian D.
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01.06.2010; Springer Nature B.V
• Subjects: Animals; Antibody Affinity; Antigens; Antigens - immunology; Biomedical and Life Sciences; Biomedicine; CD4-Positive T-Lymphocytes - immunology; Cell Biology; Encephalomyelitis, Autoimmune, Experimental - immunology; Genes, MHC Class I; Humans; Immunology; Invited Review; Ligands; Lymphocytes; Myelin Sheath - immunology; Neurosciences; Pharmacology/Toxicology; Protein Binding; Receptors, Antigen, T-Cell - metabolism; T cell receptors; Virology; functional avidity; altered peptide ligands; experimental autoimmune encephalomyelitis; MHC variant peptides; SHP-1; tolerance
• ISSN: 1557-1890; 1557-1904
• DOI: 10.1007/s11481-009-9181-3

The development of antigen-specific therapies for the selective tolerization of autoreactive T cells remains the Holy Grail for the treatment of T-cell-mediated autoimmune diseases such as multiple sclerosis (MS) and its animal model experimental autoimmune encephalomyelitis (EAE). This quest remains elusive, however, as the numerous antigen-specific strategies targeting myelin-specific T cells over the years have failed to result in clinical success. In this review, we revisit the antigen-based therapies used in the treatment of myelin-specific CD4+ T cells in the context of the functional avidity and the strength of signal of the encephalitogenic CD4+ T cell repertoire. In light of differences in activation thresholds, we propose that autoreactive T cells are not all equal, and therefore tolerance induction strategies must incorporate ligand strength in order to be successful in treating EAE and ultimately the human disease MS.