2-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 cl ass LI molecule capable of binding and forming stable complexes with a ntigenic peptide. The prototype ''beta(1)alpha(1)'' molecule included the beta(1) domain of the rat RT1.B class II molecule covalently linke d to the amino terminus of the alpha(1) domain. In association with th e encephalitogenic myelin basic protein (MBP) 69-89 peptide recognized by Lewis rat T cells, the beta(1)alpha(1)/MBP-69-89 complex specifica lly 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 an d inhibited delayed-type hypersensitivity reactions and lymphocyte pro liferation in an Ag-specific manner. These data indicate that the beta (1)alpha(1)/MBP-69-89 complex functions as a simplified natural TCR li gand with potent inhibitory activity that does not require additional signaling from the beta(2) and alpha(2) domains. This new class of sma ll soluble polypeptide may provide a template for designing human homo logues useful in detecting and regulating potentially autopathogenic T cells.