QUATERNARY STRUCTURE OF A CARRIER PROTEIN INFLUENCES ANTIGENICITY ANDIMMUNOGENICITY OF AN INSERTED T-CELL DETERMINANT

To study the influence of the quaternary structure of the outer membra ne protein PhoE of Escherichia coli on the presentation of an inserted T cell epitope, an epitope comprising amino acid residues 72-85 of my elin basic protein (MBP) was inserted at different sites in PhoE, This sequence is the critical T cell epitope in experimental autoimmune en cephalomyelitis (EAE) in Lewis rats, The antigenicity and immunogenici ty of two different conformational forms of the chimeric PhoE construc ts, i,e, the denatured monomeric form and the native trimeric form, we re studied, It appeared that the monomeric form, but not the native tr imeric form of such PhoE constructs induced proliferation of the MBP72 -85-specific i cell line Z1a, This conformational discrepancy was inde pendent of the site in PhoE in which the epitope was inserted, Immuniz ation with the monomeric form of PhoE constructs resulted in the primi ng of MBP72-85-specific T cells, In contrast, the trimeric form of the se constructs was much less efficient in priming such cells, The diffe rences between the monomeric and trimeric forms were most apparent whe n induction of EAE was studied. The monomeric form was encephalitogeni c while the trimeric form was not, Furthermore, the antigen fine speci ficity, V-beta usage and encephalitogenicity of T cells triggered by i mmunization with a monomeric PhoE construct appeared to be the same as those of T cell line Z1a, which was obtained after immunization with Map, indicating that similar cells are triggered by immunization with the epitope either inserted in PhoE or in its native context.