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.
|Original language||English (US)|
|Number of pages||10|
|Journal||Journal of Immunology|
|State||Published - Dec 1 1998|
ASJC Scopus subject areas
- Immunology and Allergy