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Regulation of Polyclonal T Cell Responses by an MHC Anchor-Substituted Variant of Myelin Oligodendrocyte Glycoprotein 35-55¹

Department of Microbiology and Immunology, Emory University, Atlanta, GA 30322

Analogs of immunogenic peptides containing substitutions at TCR contact residues (altered peptide ligands (APLs)) have been used to manipulate Ag-specific T cell responses in models of autoimmunity, including experimental autoimmune encephalomyelitis. However, recent clinical trials with APL of a myelin basic protein epitope revealed limitations of this therapy. In this study, we demonstrate that individual myelin oligodendrocyte glycoprotein (MOG) 35-55-specific T cell clones responded differentially to a MOG 35-55 APL, raising questions about the ability of peptide analogs containing amino acid substitutions at TCR contact residues to control polyclonal populations of T cells. In contrast, we found that a variant peptide containing a substitution at an MHC anchor residue uniformly affected multiple MOG 35-55-specific clones and polyclonal lines. Stimulation of polyclonal MOG 35-55-specific T cells with an MHC variant peptide resulted in the induction of anergy, as defined by a dramatic reduction in proliferation and IL-2 production upon challenge with wild-type peptide. Furthermore, treatment of T cell lines with this peptide in vitro resulted in a significant reduction in their encephalitogenicity upon adoptive transfer. These results indicate that the use of MHC anchor-substituted peptides may be efficacious in the regulation of polyclonal T cell responses such as those found in EAE.

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The JI 2003 171: 1121-1122. [Full Text]  

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