Two-domain MHC class II molecules form stable complexes with myelin basic protein 69-89 peptide that detect and inhibit rat encephalitogenic t cells and treat experimental autoimmune encephalomyelitis

We designed and expressed in bacteria a single-chain two-domain MHC class H molecule capable of binding and forming stable complexes with antigenic peptide. The prototype 'β₁α₁' molecule included the β₁ domain of the rat RT1.B class II molecule covalently linked to the amino terminus of the α₁ domain. In association with the encephalitogenic myelin basic protein (MBP) 69-89 peptide recognized by Lewis rat T cells, the β₁α₁/MBP-69-89 complex specifically labeled and inhibited activation of MBP-69-89 reactive T cells in an IL-2-reversible manner. Moreover, this complex both suppressed and treated clinical signs of experimental autoimmune encephalomyelitis and inhibited delayed-type hypersensitivity reactions and lymphocyte proliferation in an Ag-specific manner. These data indicate that the β₁α₁/MBP-69-89 complex functions as a simplified natural TCR ligand with potent inhibitory activity that does not require additional signaling from the β₂ and α₂ domains. This new class of small soluble polypeptide may provide a template for designing human homologues useful in detecting and regulating potentially autopathogenic T cells.